Sunlight and the circadian rhythms in your skin

SUNLIGHT entrains circadian rhythms.  It gives us vitamin D and melanin; it can give us a sunburn, but some evidence suggests that it does NOT cause skin cancer.

“lifetime sun exposure appeared to be associated with a lower risk of malignant melanoma” (Kennedy et al., 2003)

Anecdotally (or so I’ve heard), skin cancer frequently develops in places not regularly exposed to sunlight.  If true, this flies in the face of the dogma which goes something like this (Tl;dr): ultraviolet light from the sun penetrates into the nuclei of skin cells and damages DNA; if the right [wrong] genes are altered/mutated and the mutated cells proliferate, it can develop into a tumor (gross oversimplification).

So, what might explain the discord?

LIGHT entrains the circadian clock; this includes regulating cell cycle genes.  Aberrant cell cycling may lead to out-of-control proliferation in the wrong context, aka cancer.  Interestingly, some evidence suggests that part of the circadian regulation of cell cycle genes includes turning down proliferation when exposure to UV light is expected to be high (daytime); so DNA repair machinery has more time to fix any cell cycle genes that are mutated by UV light before the cell proliferates (Geyfman and Andersen, 2009) = lower chance of creating and propagating a potentially cancerous skin cell.

 

 

Another thing is that DNA repair mechanisms in the skin are upregulated, in circadian fashion, during the day (perhaps directly via bona fide clock genes).

 

Running for time: circadian rhythms and melanoma (Markova-Car et al., 2014) 

 

Sunblock = less potentially damaging UV?  Sunblock prevents sunburn, but does it reduce skin cancer?  Studies are mixed on this; however, skin cells NEED to proliferate… perhaps doing so at night (as would occur with proper circadian signaling) is the simple solution.

 

Are some melanomas caused by artificial light? (Kvaskoff and Weinstein, 2010)

The incidence rate of cutaneous melanoma has been increasing faster than that of any other cancer in white-skinned populations over the past decades. The main risk factors for melanoma (i.e. exposure to sunlight, naevus count, phototype, and family history of melanoma) may not wholly explain the epidemiological trends observed for this cancer. The light-at-night theory postulates that increasing use of artificial light-at-night may contribute to the increasing breast cancer incidence through suppressed secretion of melatonin (a hormone produced in the dark and inhibited by light, which regulates circadian rhythms). Here, we postulate that this theory may also apply to melanoma and that it may explain a part of this cancer burden. Consistent with our hypothesis is evidence from experimental studies suggesting a lightening effect of melatonin on frog skin and mammal hair during seasonal changes, its antioxidant and anti-carcinogenic effects in skin melanocytes, as well as the expression of melatonin receptors in melanocytes. Also, epidemiological data suggest lower melatonin concentrations in melanoma patients compared with controls; a potential therapeutic effect of melatonin in patients with metastatic disease; a higher prevalence of melanoma in pilots and aircrews, with increased risks with higher time zones travelled; and increased melanoma risks in office workers exposed to fluorescent lighting. Moreover, melanoma incidence and seasonal patterns are consistent with a reduction of melatonin secretion with intensity of exposure to light, although it remains difficult to distinguish the effect of melatonin disruption from that of sun exposure on the basis of ecological studies. Finally, the reported associations between hormonal factors and melanoma are consistent with melatonin inhibition increasing the risk of melanoma by increasing circulating oestrogen levels. Despite the existing suggestive evidence, the light-at-night hypothesis has never been directly tested for melanoma. Very few studies examined the potential associations between melanoma risk and shift work or melatonin concentrations, and we found no studies reporting on the relationship between melanoma and number of sleeping hours, use of melatonin supplements, blindness, night-time city light levels, bedroom light levels, or clock genes polymorphisms. Therefore, since several observations support our hypothesis and very little research has been undertaken on this subject, we strongly encourage analytic epidemiological studies to test the light-at-night theory for melanoma causation.

 

 

All of this suggests to me: get unadulterated sunlight during the day; and there’s not a whole lot of UV in devices like iPads and smart phones, but there IS a lot of circadian rhythm-disrupting blue light which may shift the proliferation of skin cells such that less is occurring at night and more during the day.  So it’s not the UV per se, but rather a circadian mismatch.

 

Some of this is speculation, and is assuming that at least part of the circadian regulation of skin cell cycle genes is mediated centrally via SCN, but it could also explain the discord regarding sunblock and skin cancer… also, it’s important to keep in mind that circadian biology is a fully integrated system (it controls just about everything).

 

Nix the sunblock and avoid artificial light (as much as possible); enjoy natural sunlight (as much as possible)… and break your fast in the morning (to entrain peripheral with central clocks).

 

 

Premature skin aging (wrinkles, sun spots, etc) is probably a real phenomenon due to excess skin tanning and sun bathing, so don’t do that… but don’t avoid regular exposure to sunlight.

 

calories proper

 

Be Sociable, Share!
Share
  • Jack Kruse

    You said, ” Some of this is speculation, and is assuming that at least part of the circadian regulation of skin cell cycle genes is mediated centrally via SCN” You’re not speculating. The SCN is the king. The experimental evidence also clearly indicates that the retinal circadian clock network is hierarchically organized to control the entire organism and not just SCN. HIERARCHICAL CONTROL MEANS IT CONTROLS THE ENTIRE ORGANISM. GAME, SET, MATCH. That means nothing is more important to a living thing. Today’s humans have created a world and environment that is dominated by blue light emission night and day! Blue light destroys DHA presence in mammalian cell membranes everywhere in our tissues. The destruction of the retina however is the most important, because the eye clock controls the flow of carbon in every cell of our body. The flows of carbon are directly tied to how well our mitochondrial respiratory proteins work in concert with nuclear DNA. As DHA levels decline, the inputs to the SCN from melanopsin photoreceptors also decline. This degrades the optics of the atomic lattice in the SCN that responds to 460-500 nm light. This is in the blue range. This causes cells to age faster by raising their ubiquitin rates. Simultaneously it lowers NAD+ levels in cells. KEY POINT: As NAD+ lowers, so does the entire cell redox potential. This selects for specific mitochondrial respiratory protein changes as they key factor in aging, heart disease, and oncogenesis. Skin cancer is a form of oncogenesis. What are those changes we do have evidence for ALREADY? Normally the length of the respiratory chain in mitochondrial is 60 Angstroms. When NAD+ is lowered the length of the respiratory chain increases. Every Angstrom it increases slows electron tunneling in mitochondria down by a FACTOR of TEN!!! This alters how electrons can flow in electron chain transport and affect oxygen levels in cells. Another great blog Bill. Let me ask you something: When do you think the world will realize that light is the most powerful drug for an animal with mitochondria?

    • http://www.caloriesproper.com/ Bill Lagakos

      “When do you think the world will realize that light is the most powerful drug for an animal with mitochondria?”

      Dude, I think we’re moving in the opposite direction at a very rapid pace.

  • TechnoTriticale

    re: … dogma which goes something like… damages DNA; if the right [wrong] genes are altered/mutated and the mutated cells proliferate, it can develop into a tumor (gross oversimplification). So, what might explain the discord?

    As Jack’s response suggests, another part of the explanation is that the somatic (gene) theory of cancer is almost certainly incorrect, with the metabolic (Warburg/Seyfried) being the leading contender for replacing it. The metabolic theory looks at mitochondrial damage as the trigger.

    If there’s light-based circadian activity in the skin (or under it – the skin is translucent), the take home (literally) is: blue blockers aren’t a complete fix for a lifestyle out of sync with the sun. The Philips Hue and GE Align bulbs start looking a lot more interesting (as does merely respecting the clock).

    • Jack Kruse

      Well I think Warburg and Seyfried effect are miscast right now and have said as much on my blog. The Warburg effect is a sign a mitonuclear asynchrony and I do think it is an example of a serious circadian mismatch. I do not believe Seyfried is 100% about his belief about ketosis as being the optimal Rx for this condition. Ketosis will lead to apoptosis……and for optimal tissue functioning in heart and brain we want autophagy and not apoptosis.

      • Jack Kruse

        Cancer as a mitonuclear asynchronous disease? http://ow.ly/Ocpj2

      • Ray

        So the Ketogenic diet I pursued coupled with Vit D each morning for two years prior to developing Esophageal Gastric Junction cancer was a potential contributer? And the the continued use use of the Ketogenic Diet to offset lean body mass loss is counter productive?

        • Jack Kruse

          Ray it is more detailed then that. The type of ketosis you use with cancer is quite important. It must have a lot DHA in its creation to help repair the defect in circadian eye clock. http://www.jackkruse.com/organization-structural-failure-8-ketosis-appears-fail/

        • doctorsh

          Just n=1 experience along with those of many in my practice, but taking VitD at night appears to help with sleep, perhaps by helping reset circadian rhythms, melatonin, or some other variable.

          Bill?

          • http://www.caloriesproper.com/ Bill Lagakos

            no effects of vit D supps on sleep that I know of

          • doctorsh

            Ok. Then let’s attack this another way.
            What part of the day do Vitamin D levels peak?
            Where is Vitamin D involved in circadian rhythms?

            I advise my patients, if needed, to take vitd3 supplement dinner to bedtime as a great percentage get better more restful sleep.

            I am still waiting for the possible mechanism of action so perhaps a circadian rhythm author and researcher can help figure this out. ????

          • http://www.caloriesproper.com/ Bill Lagakos

            I honestly don’t know the pharmacokinetics of endogenously synthesized vitamin D — minutes after peak sun exposure? hours? days?

            That said, I haven’t seen anything in the literature showing improved sleep w/ D supps at night; could be placebo…
            I know I know, people hate hearing that sorry :-)

          • doctorsh

            It’s not placebo.
            It works for me and many others but not in everyone.
            As I say to many learned people, just because we don’t know how it works, does not make it placebo or quackery.
            Just a mystery to be solved.

          • daz

            when i looked in to this a while ago (vitamin D & diurnal rhythm), i did find one related study. i’ll post the info/link in a separate comment.
            I do believe that supplement with D3 can influence sleep, both acutely (timing of dose) & chronically (whether you have a deficiency or not).
            Anecdotally, in my case, supplement with D3 in the evening or before bed makes my sleep worse. When i looked in to this further (google), there ere plenty of other similar stories.
            I now supp with D3 every day between 9am & 10am on the presumption that there may be a related diurnal rhythm…so best to supp at approx the same time every day.

          • daz

            & here’s the related study;
            It relates to plasma levels of 1,25(OH)2D.

            “Diurnal rhythm of plasma 1,25-dihydroxyvitamin D and vitamin D-binding protein in postmenopausal women…” http://www.ncbi.nlm.nih.gov/pubmed/11980618

            Objective: Diurnal variations in plasma levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) have previously only been investigated in young individuals, and these studies have failed to demonstrate a diurnal rhythm. We have studied whether plasma levels of 1,25(OH)(2)D and vitamin D-binding protein (DBP) vary in a diurnal rhythm in postmenopausal women.

            Results: Plasma 1,25(OH)(2)D exhibited a diurnal rhythm (P<0.01) with a nadir in the morning (99+/-12 pmol/l), followed by a rapid increase to a plateau during the day (113+/-13 pmol/l, i.e. 14% above nadir level; P=0.005). A similar pattern of variation was found in plasma levels of DBP with peak levels 15% above nadir levels (P<0.01). The free 1,25(OH)(2)D index did not vary in a diurnal rhythm. PTH and plasma levels and urinary excretions of calcium and phosphate exhibited a diurnal pattern of variation. The diurnal rhythm of DBP was correlated with the rhythm of 1,25(OH)(2)D (r=0.47, P<0.01) and plasma albumin (r=0.76, P<0.01). Moreover, the rhythm of plasma calcium and PTH varied inversely (r=-0.36, P=0.02).

          • http://www.caloriesproper.com/ Bill Lagakos

            thanks for the link!

            seems like there’s not a huge range, 14% increase from bottom to top… probably also impacted by sun exposure & dietary intake.

          • daz

            yep, i would agree, it would be affected by sun (uvb) and foods.
            if you were able to keep the study participants ‘locked’ in a windowless room for 24 hours with no changes to light conditions (& no uvb) & no changes to exposed skin area…
            my guess would be the line would not rise much from the morning baseline…perhaps some small blips post meals.

          • daz

            link to pdf of full study here;

            http://eje-online.org/content/146/5/635.full.pdf

      • TechnoTriticale

        re: I do not believe Seyfried is 100% about his belief about ketosis as being the optimal Rx for this condition.

        I’m not clear on your point there, but if you haven’t seen it, the latest paper on which he is co-author was published just a few days ago:
        http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0127407
        It’s not just KD, and isn’t even KD-R. Caution: mice.

        Details of the KD used were not provided, and I can’t find anything on “KD-USF” on the Harlan Labs site. It was most likely not HL’s standard KD (TD.96355) as that’s mostly Crisco (yikes). So we don’t have any idea what DHA dose might have been involved.

        I read Seyfried’s book when it was published in 2012, and figured that if it were THE answer, we’d know pretty quickly. It’s clear 3 years later that it’s helpful, but is not the whole answer (and may even be digging an incorrect theory hole), but people are using KD as a holding action on some intractable cancers, and there are startling remission anecdotes from time to time.

        Does a mitonuclear asynchrony approach suggest actionable therapies?

        • http://www.caloriesproper.com/ Bill Lagakos
          • TechnoTriticale

            re: The “KD-USF” was published here:

            Thanks. Looks like it’s predominantly MCT, and the only Omega 3 would be mostly ALA. So unless mice are really efficient at ALA conversion, no DHA to speak of.

            The stated goal of the diet development was silent on n3. Based on what I saw about Teklad’s (Harlan’s) own mouse KD, I’m not sure I would have asked for their advice at all.

            DHA in the mouse KD for cancer research might be seen as either an overlooked enhancement or a deliberately omitted material confounder.

          • http://www.caloriesproper.com/ Bill Lagakos

            most rodent diets don’t have any added DHA… they can “get by” with vege-n3’s. But most still think vege-n3’s are the actual essential ones :/

            http://caloriesproper.com/vegetable-oil-fatty-acids-are-not-essential/

            nope

    • http://www.caloriesproper.com/ Bill Lagakos

      Hue & Align look cool…
      also need to get kids off their iPads & smart phones at night (or at least Twilight/F.lux + blue blockers)… “respecting the clock”

      • doctorsh

        Bill
        Any iPad or iPhone apps that work to block blue light?

  • CynicalEng

    England’s NHS spent $120m on vitamin D supplements in 2013 – the fifth biggest spend on a single compound. Metformin was #4. Keep up the good work and I’m off out into the sun……

  • Pingback: Tedenski pregled #7()

  • http://www.caloriesproper.com/ Bill Lagakos

    “Scientists Blow The Lid on Cancer & Sunscreen Myth” http://bit.ly/1Jb21Cn

    • TechnoTriticale

      re: Nix the sunblock …

      2008: Tumorigenic Effect of Some Commonly Used Moisturizing Creams when Applied Topically to UVB-Pretreated High-Risk Mice
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630214/

      re: Premature skin aging (wrinkles, sun spots, etc) is probably a real phenomenon due to excess skin tanning and sun bathing, …

      In other contexts, tanning is understood to be the process of turning skin into leather.

      re: … so don’t do that… but don’t avoid regular exposure to sunlight.

      Anecdotally, I used to be highly susceptible to sunburn, and either avoided sun, or lathered up before exposure. Diet was SAD, evolving to Zone. Sometime after switching to LCHF low-inflam grain-free, I stopped using sunscreens due to concerns about their chemistry. I was surprised to discover that my propensity to sunburn had vanished. This diet is coincidentally high in DHA&EPA. Cause&effect? Who knows. I like this outcome and am not inclined to challenge test it.

      • http://www.caloriesproper.com/ Bill Lagakos

        “This diet is coincidentally high in DHA&EPA. Cause&effect?”

        Dunno, but I’m adding it to my bank of diet/lifestyle-related suntan/sunburn anomalies (which is growing at a pretty high rate).

      • http://carefactorcritical.blogspot.com.au/ Spittin’chips

        I add my n=1 to this experience. Where I live, the sun is Harsh. Some days when I was younger led to burns so bad, the skin blistered. Proper blisters. This wasn’t from me sunning myself on the beach either, it was days fishing or at a school sports day when I’d forgotten to bring sun cream. I therefore have a big problem with health gurus who pronounce we should all throw away the creams – they have their place. Although I don’t burn anywhere near as badly these days, I do slap some on when I know I’ll be a few hours out on a boat. Curious to know what the diet link is though.

  • Pingback: Zdrowa dawka s?o?ca. Cz. I | Paleo zdrowie()

  • Pingback: Paleophil's Journal of Random Thoughts - Page 13 | Mark's Daily Apple Health and Fitness Forum page 13()