The incredible camping experiment, circadian proper

Entrainment of the Human Circadian Clock to the Natural Light-Dark Cycle (Wright et al., 2013)

Abstract (edited): The electric light is one of the most important human inventions. Sleep and other daily rhythms in physiology and behavior, however, evolved in the natural light-dark cycle, and electrical lighting is thought to have disrupted these rhythms. Yet how much the age of electrical lighting has altered the human circadian clock is unknown. Here we show that electrical lighting and the constructed environment is associated with reduced exposure to sunlight during the day, increased light exposure after sunset, and a delayed timing of the circadian clock as compared to a summer natural 14 hr 40 min:9 hr 20 min light-dark cycle camping. Furthermore, we find that after exposure to only natural light, the internal circadian clock synchronizes to solar time such that the beginning of the internal biological night occurs at sunset and the end of the internal biological night occurs before wake time just after sunrise

In other words, they compared circadian events during 2 weeks of normal life to 2 weeks of 100% camping.  And camping won.

Camping vs. Light exposure
All of these things are somewhat obvious, I just thought it was cool that it was actually measured.

Regular week: 979 lux from artificial lights, TVs, iPhones, sunlight, etc.  Just think of this “lux” as baseline, or how much light you are exposed to on a daily basis.

Camping: 4487 lux from sun and campfires.

Similarly, total light exposure was 3-4x higher when camping probably because it is 100% sunlight – no kitchens, dimly bedrooms, windows, or dark hallways.


Apparently, morning is the most important time of day to get good light exposure, just as evening is the most important time to get no light exposure.  And somewhat humorously, evening light exposure was 2-3x greater during normal life (note the ordinate): light exposure

Melatonin
Regular week: melatonin  onset @ 10:30pm, sleep @ 12:30am; melatonin offset & wake-up @ 8am.

Camping: everything occurred 2 hours earlier, even though they only went to bed about an hour earlier.  So, melatonin started increasing ~3 hours prior to bedtime.  Sleep duration was the same in both conditions.  Melatonin onset magically timed up with sunset, ie, circadian proper; and melatonin offset occurred prior to waking up <– that seems important… groggy in the morning?  The authors noted that in general, “the circadian low point in brain arousal, as defined by cognitive performance level or physiological markers of sleepiness, occurs after habitual wake time, near to the timing of melatonin offset.”  When camping, melatonin offset occurred 50 minutes prior to waking up.  Can you intellectually conceive an altered universe where you have absolutely no desire for coffee in the morning?melatonin

Part 2.
What comes first…  Corbalan-Tutau (2012) showed that people with metabolic syndrome had lower evening melatonin levels and lower morning cortisol levels. (I bet a camping trip would do them some good.)mel & cort

Tyrosine hydroxylase, an enzyme involved in dopamine synthesis, is also light-sensitive (de Lima 2011): high in the morning –> declines all day –> and is then reactivated at night, theoretically to recharge for high morning dopamine levels.Tyrosine hydroxylase

And I’m just going to assume that this too is perturbed in metabolic syndrome, thus why bromocriptine is efficacious here.   Perhaps camping would fix this, too.

None of these findings bode well for submariners, astronauts, or even shift workers.  Probably doesn’t apply too much to the former two, as they are generally healthier than average to begin with.  But shift workers… unless you’re like Ben Morgan or Jane Plain, who are mindful of the importance of light exposure, sleep, and diet, then you might want to consider paying attention.  In a report by Straif (2007), shift work was deemed a “probable” cause of Significant Morbidity.


Melatonin vs. insulin sensitivity
Disclaimer: I’m very possibly losing sight of the forest for the trees (wouldn’t be the first time)…

Spurred on by a comment from Jane Plain in last week’s post, I decided to reassess melatonin (see comment for background info).  My conclusion: the effects of plain old melatonin on the metabolic condition seem utterly disconnected those of circannual melatonin rhythms proper.

Observational data:
Melatonin secretion and the incidence of type 2 diabetes (McMullan et al., 2013)
Nurses’ Health Study: Most of the info in the table below is known: the women who later went on to develop diabetes were heavier, sedentary, inflamed, and insulin resistant.  But they also had significantly lower melatonin:

McMullan 1And when the whole group was combined and divided into tertiles of melatonin secretion, high melatonin secretion is also associated with insulin sensitivity (and  to take a cheap shot at ELMM –> BMI was linearly though statistically non-significantly related to physical activity :P )

McMullan 2

These findings were confirmed in the Nurses’ Healthy Study II cohort (McMullan et al., 2013)

Intervention (ie, better) data:
Plasma [hormonal] response in NASH patients treated with melatonin (Gonciarz et al., 2013)

Odd treatment regimen: 5 mg melatonin at 9am and another nickel at 9pm, for four weeks.  Liver enzymes improved.  NASH patients are insulin resistant but do NOT have lower melatonin levels… although pharmacologically enhanced melatonemia (~4x increase) reduced insulin & insulin resistance (and increased leptin).NASH melatonin

Another intervention study, and this one was an almighty crossover (albeit not a very good one): Garfinkel et al., 2011.  Diabetic insomniacs treated with 2 mg prolonged-release melatonin  2 hours prior to bedtime for 3 weeks.  Result: No change in fasting blood glucose, but HbA1c declined by about 1 percentage point.  N.B. 2 mg at night is quite different from 5 mg BID.

These findings are amply supported by animals studies, but my gut produces 500x more melatonin than my brain and it tells me animal studies may not fully replicate the human circadian condition.  Soapbox: dodgy evidence that supports your theory is still dodgy evidence even though it supports your theory.  I’m not saying all animal studies are bollixed, I’m just saying this particular topic is very nuanced.  Laboratory mice reside in a small temperature & light-controlled box and usually only live through one circannual voyage if their lucky (unlucky?).  End soapbox.


Possible reconciliations: 1) Perhaps autumnal waxing melatonin levels exert tissue-specific effects on insulin metabolism geared to promote body fat growth…  2) Alternatively, perhaps oral melatonin is different from brain melatonin (eg, local antioxidant effect on liver, etc.), although not sure how this would account for the reduced “melatonin secretion” seen in McMullan’s pre-diabetics.  But 3) maybe urinary melatonin metabolites reflect gut melatonin and have nothing to do with brain melatonin.  Given the abundance of alternate explanations, I’m beginning to think this is a rabbit hole I shouldn’t have wandered down.

Edit:

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  • George

    That’s it, I’m gonna buy a tent.

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

      +1!

      when I lived in San Diego, I used to sleep on my balcony all the time; however, this was probably fully negated my glaring laptop… perhaps it’s time to look into those blue light blocking computer monitor screens.

      Adverse health effects of nighttime lighting: comments on american medical association policy statement.
      https://www.ncbi.nlm.nih.gov/pubmed/23953362
      The AMA House of Delegates adopted a policy statement on nighttime lighting & human health. This major policy statement summarizes the scientific evidence that nighttime electric light can disrupt circadian rhythms in humans and documents the rapidly advancing understanding from basic science of how disruption of circadian rhythmicity affects aspects of physiology with direct links to human health, such as cell cycle regulation, DNA damage response, and metabolism. The human evidence is also accumulating, with the strongest epidemiologic support for a link of circadian disruption from light at night to breast cancer. There are practical implications of the basic and epidemiologic science in the form of advancing lighting technologies that better accommodate human circadian rhythmicity

      • red screen warrior

        No need to buy a new monitor, there is a program called “f.lux” that adjusts the Blue of your screen depending on time of day. There’s also one for Linux called redshift, and various apps for Android and iphones that accomplish the same.

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

          Thanks for this. Lot of cool studies about artificial light exposure, sleep, and circadian rhythms on their website (http://justgetflux.com/research.html)… but unfortunately no studies on their product [yet]. Seems promising, though.

          Found this:
          Suppression of melatonin secretion in some blind patients by exposure to bright light.
          http://www.nejm.org/doi/pdf/10.1056/NEJM199501053320102 (free full text).

          • http://itsthewooo.blogspot.com/ Jane Plain (Woo)

            not only does the eye program the scn, but the skin is capable of detecting light and responding with melatonin suppression… even a small patch of skin exposed to light can do this. Shift workers have no chance lol.

  • http://itsthewooo.blogspot.com/ Jane Plain (Woo)

    This was fabulous Bill.

    Interesting anecdote, remember TEH GREAT HURR-CAIN SANDY of NJ last year? After a few days of almost total abstinence of fake light I began sleeping at night, winding down with sun down, and waking in the morning and feeling more energetic/invigorated. I didn’t even totally abstain from artificial light (I was still going to work in the evening) but there was a clear trend to normalizing circadian clock with the sunlight. It was fascinating and right away illustrated how much of modern disease is related to artificial light (which is really a very novel invention only a few decades).

    I suspect much of the chronic fatigue I feel working dedicated night shift is related to loss of the circadian pattern of dopamine/NE – tyrosine hydroxylase.
    Not seeing that bright sunlight early in the day promotes a constant lethargy independently contributing to low motivation and weight gain. On the other hand, melatonin is lower as well (and light therapy can suppress it further) but energy is simply lower I find, even if you sleep a ton. When I do see a lot of light when I wake up (ONLY POSSIBLE in june and july) my energy patterns are more like they are when I am sleeping / waking earlier with the sun. Light therapy can help but it is no match for what sunlight can do.

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

      Sunlight > artificial light. It is known.

      “I didn’t even totally abstain from artificial light” <– bodes well for the human race, as total abstinence is unlikely ever.

  • http://itsthewooo.blogspot.com/ Jane Plain (Woo)

    The melatonin story (sorry in advance, very long :( ):

    With regard to melatonin and met syn, melatonin is one of those hormones where in excess it tends to promote energy conservation states, but when deficient is much more significantly suggests – and causes – disease.

    A problem with many studies WRT melatonin is isolating the circadian rhythm normalizing effect of this substance from the actual specific effects of the hormone. It seems that scientists use rats fed high fat diets to test an “obesigenic” condition, and the rats often exhibit disrupted circadian patterns as the unnaturally higher fat diet tends to promote frequent eating over a 24 hr period with this diet. In these examples using melatonin is body-normalizing for the rats, health parameters improve in accordance with regularizing body rhythms. I don’t have reference but I believe it has been suggested some of the “high fat diet induced wt gain” relates to circadian rhythm disruption induced by the unnaturally high fat diet (the rats stop sleeping in daytime normally).

    A feature of sleep deprivation, and lack of normal “offset” of circadian day / start of circadian night with melatonin surge , as might occur to a rat in a scientific study eating a high fat diet, is that the sympathetic nervous system and HPA axis – cortisol – is always active. Melatonin specifically shuts off the SNS and cortisol, the latter of which is potently adipogenic directly stimulating adipogenesis and also driving insulinemia sufficient for this to occur. In this instance the melatonin is not so much weight reducing as it is normalizing the bodies of the rodents against this very unnatural intervention of disrupted sleeping and feeding patterns.

    The SNS tends to inhibit body fat but it very potently drives insulin resistance and diabetes if already present. Inhibiting/normalizing an overactive SNS may indirectly help weight in such cases of a hyperactive SNS with insulin resistance.

    However, melatonin itself, apart from circadian regulating effect, is quite uncontroversially a thrifty hormone. Melatonin bias of the nerouendocrine system occurs in states of anticipatory or actual nutrient deprivation. During acute starvation the CNS biases to melatonin dominance, and during anticipatory season shift to death (winter) this also occurs. The function of this is to promote increasing energy thrift and weight gain as fat. This is accomplished by reducing reproductive hormones, thyroid hormones, and suppressing the SNS and HPA axis excessively to a state of deficient energy production.

    Here is a study of seasonal obese animals and how mel administration (relative increase in mel) triggers symptoms:
    http://www.ncbi.nlm.nih.gov/pubmed/12954394

    Long photoperiod actually prevents weight gain by suppressing mel.

    There are a few things to consider here with regard to melatonin:

    1) The two very distinct conditions of DIABETES and OBESITY. These diseases are often spoke of together as if the treatments are exactly the same, but this is not true. Things that help diabetes often make obesity worse, and vice versa; diabetes can be thought of as the disease that happens when obesity stops, and triggering obesity can often help blood sugar control and diabetes (e.g. PPARy agonist drugs, or the natural surge of adiponectin post starvation, promote new fat cell growth and blood sugar/insulin will decline accordingly )

    For example thyroid hormone treatment and sympathetic stimulants (things which melatonin suppresses) will reduce fat mass and increase energy *but* will also worsen blood sugar and diabetes. On the other hand, sympathetic suppressive interventions will help diabetes, but tend to cause weight gain and lethargy.

    Melatonin is a sympathetic suppressive, thyroid hormone suppressive intervention, and when levels are NORMALLY increased in the context of sufficient levels (as with a shortened photoperiod) this endocrine change will cluster with lethargy , weight gain, reduced fertility and other energy conservation symptoms.

    2) The second thing to consider is the difference between deficiency vs excess; many people who are obese, with insulin resistance, are suffering from circadian rhythm disruptive disorders, or perhaps they have methylation defects and neurohormones like melatonin – which are already deficient – are additionally not working properly in their body. Even though melatonin tends to progressively promote an energy conservation state independent of all other factors, it ALSO serves a dual role of regulating the circadian system and orchestrating hormone patterns in logical fashion, and even inhibiting insulin resistance secondary to this. Indirectly, the lack of melatonin promotes met syndrome and obesity secondary to circadian dysregulation, and in such instances the melatonin may be helpful , particularly to control diabetic changes to blood sugar.

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

      Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet.
      http://www.ncbi.nlm.nih.gov/pubmed/22608008

      While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed a HFD ad lib eat frequently throughout day & night, disrupting the normal feeding cycle. To test whether obesity & metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8hr/d. Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, & inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, & AMPK pathway function and oscillations of the circadian clock and their target genes’ expression. These changes in catabolic & anabolic pathways altered liver metabolome & improved nutrient utilization & energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.

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

      so much fodder for future blog posts in this comment ?
      +1

  • http://itsthewooo.blogspot.com/ Jane Plain (Woo)

    TLDR: I tend to think a loss of melatonin is a sign for disease/aging and melatonin can be health promoting metabolic normalizing in these instances.

    Assuming a baseline state, however, endocrine bias to melatonin follows with inhibition of energy wastefulness , increased energy thrift, symptomatically signs of SAD like lethargy hypersomnia hyperphagia and weight gain.

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

      Awesome “TLDR”

      “Melatonin bias –> inhibition of energy wastefulness.” Seems like a good thing to keep in mind when I’m re-reading your longer comment (above).

      Interesting, too, that similar to inflammation, melatonin can dissociate weight gain from insulin resistance. sort of.

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

    Not like we needed it, but here is a reason to refrain from daytime drinking:

    Melatonin inhibits alcohol-induced leaky gut & intestinal permeability in rats in vivo.
    http://www.ncbi.nlm.nih.gov/pubmed/23639810

    Alternative interpretations: better to imbibe outside, while camping, and in winter.

    (disclaimer: this could theoretically be a gut vs brain-derived melatonin thing, such that high oral doses will do it but darkness won’t.)

    • http://ashsimmonds.com/ Ash Simmonds

      On the other hand, alcohol appears not to affect melatonin secretion or circadian rhythms too much in a non-alcoholic (“continuous consumption of large amounts”): http://www.ncbi.nlm.nih.gov/pubmed/16679342

      On this I would suggest that evening drinking is actually a reasonable counterbalance to modern life under artificial light as it allows us to obtain “naturalish” sleep sooner than we might otherwise.

      Therefore the rule should be: don’t drink unless you are in front of a screen – and NEVER sit in front of a screen unless you have a drink! :D

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

        holy shit if it weren’t for the study you linked I would’ve sworn you were quoting something from the film Idiocracy.

        Love that conclusion, btw. (but still considering looking into f.lux or something similar)

        • http://ashsimmonds.com/ Ash Simmonds

          Have read some of the f.lux stuff before along with a whole bunch of anecdotal testimonials.

          Never tried it but reading about it made me realise I’ve always kinda done that – typically keeping artificial lighting as low as possible and using low light profiles on the telly after dark, and when I read books on my phone in bed I put the light down to the lowest setting so my eyes have to struggle. However my laptop I haven’t bothered messing with at this stage…

          I lived a bunch of time in the country growing up, for a while there without electricity and all that jazz, so living by campfire and candlelight is pretty well ingrained. Or maybe I was just a pyromaniac.

          • http://ashsimmonds.com/ Ash Simmonds

            Ok, just downloaded f.lux – incredibly simple, and within a minute of use of my laptop sitting in a room at ~1am with a 15w yellowish globe it actually already does seem about right.

            Gin is there as a backup plan.