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Circadian Rhythms: Zeitgebers, Entrainment, and Non-Photic Stimuli

Posted By Mark Sisson On July 21, 2010 @ 12:37 pm In Health,Sleep | 38 Comments

For all the unchecked randomness in this world, there are at least some things you can count on. The sun always rises and it always gets dark, and that’s something life – all life – has learned to rely on. Our internal clocks, known as circadian rhythms, tend to match up with this established external cycle. In essentially all known forms of life, from the earliest cells and bacteria to plants and mammals, the circadian rhythm is characterized by a period of around 24 hours.

You might recall a previous MDA series on how blue light can affect our circadian rhythms [7], and what we can do to maintain normal, natural levels and timing of blue light exposure. Long story short – it turns out that our exposure to blue light is akin to exposure to daylight, and getting too much – or too little – at the wrong times can disrupt our natural circadian rhythm and affect the quality of our sleep by changing when melatonin is secreted in our bodies. In other words, blue light is a major human zeitgeber (the ten-dollar word of the day); an exogenous [8] cue that synchronizes our internal clock. But it’s not just light that affects our circadian rhythms.

The master mammalian circadian pacemaker is located in the hypothalamus, in a section known as the suprachiasmatic nucleus (SCN). Lesser circadian pacemakers with their own 24-hour cycles, sometimes called slave oscillators, have also been located in the eyes, pineal gland, liver, intestines, and other organs, but the SCN is said to synchronize them [9], employing over 20,000 neurons in the process. The SCN receives input via three main pathways: the retino-hypothalamic tract, which directly delivers photic (light-derived) information; the geniculo-hypothalamic tract, which indirectly delivers photic information; and the raphe-hypothalamic tract, which uses serotonin to deliver non-photic information to the SCN. The SCN tells the pineal gland to secrete melatonin. Both photic information (like blue light) and non-photic information (like temperature, social cues, food availability, to name a few) act as zeitgebers with the ability to entrain (circadian synchronization in accordance with an outside cue is called entrainment) internal clocks. We’ve already covered the photic side of things (which also happens to be the most powerful), so let’s take a look at how some non-photic zeitgebers affect your internal clock and what you can do to entrain your own circadian rhythm.

Feeding

Just as the sun rises and falls, the availability of food come in cycles, too. Indeed, research suggests that food availability cycles entrain organisms’ circadian rhythms. The classic example is the “early bird” who “gets the worm.” How does it “know” to wake up at the hour most advantageous? The bird doesn’t actively plan to wake up at a certain time and head out for grub(s). The availability of the food (in this hypothetical case, early morning) conditions the bird’s circadian rhythm to prompt an early morning wakeup. We see this in rodent models [10], which display distinct “food anticipatory activity” in the hours just before their regular mealtime, even if the SCN is damaged or removed, offering evidence [11] of a separate, independent “food-entrainable oscillator” that responds to food intake schedules. We see similar results in mammal [12] and primate [13] studies.

As for humans, food-modulated C-peptide [14] increases correlated with reductions in melatonin [15], the “sleep hormone”. In another study, patients with night eating syndrome (those folks who eat in their sleep) also showed [16] delayed melatonin secretion. (Side note: They also showed delayed circadian onset of hunger-blunting leptin [17] as well as advanced circadian onset of hunger-stimulating ghrelin secretion. Leptin release was delayed by one hour and ghrelin was bumped up five hours! Eating at night may have weight-gaining implications, but this is another post entirely). Eating late at night can phase shift your circadian rhythms [18] by blunting melatonin secretion. So if you’re having a tough time sleeping consider not eating too late.

Exercise

In animals, activity levels affect circadian rhythm. Using body temperature regulation as an indicator of circadian phase shifts, we see evidence [19] of the zeitgeber effect of physical activity in nocturnal animals put on a daytime activity schedule. Whereas nocturnal animals typically have high body temperatures and activity levels at night, forcing them onto a diurnal activity schedule causes body temperature to rise during the day and fall during the night. Their circadian rhythms are adjusting to the new schedule.

Evidence on exercise’s circadian effects in humans is less conclusive, but still present. One study [20] identified nightly exercise (three 45-minute bouts of cycling) as an effective phase delayer of melatonin/sleep onset, and another [21] showed similar results. One group of researchers was able to effectively convert night workers onto a daytime sleep schedule [22] by controlling light input and using hourly bouts on the bike to phase delay the onset of circadian melatonin and body temperature rhythms. Strangely, one study [23] showed that evening and nocturnal exercise actually resulted in melatonin increases, or advances in circadian phases – I wish the authors had given details on the exercise protocol so we could understand the apparent anomaly. Still, most studies [24] do show that delaying the onset of circadian melatonin rhythms is achievable through exercise. Whether that’s a desirable outcome is up to you to decide. Night workers may want to play with nocturnal exercise.

Social Cycles

Can interactions between organisms cue circadian entrainment? Most likely. Researchers generally agree that circadian clocks developed primarily in response to the daily cycles of the environment – and, for most organisms, the environment includes not just light, dark, and temperature, but also the rhythms of and interactions with predators, prey, parasites, and community. For example, when two previously isolated deer mice, each with a different circadian rhythm, were placed in a common enclosure, they developed a mutual synchronization of their internal clocks [25]. Honeybees forage in synchronicity with the rest of their colony, but isolated members tend to drift away from established foraging schedules, suggesting an important role for social entrainment. Members of numerous species show signs of metabolic synchronicity when in close contact with each other, including honeybees [26], beavers [27], bats [28], and even humans [29]. In fact, something called the Social Rhythm Stability Hypothesis proposes that disruptive social events (deaths, break-ups, even minor disturbances of a person’s normal routine or of those around them) can entrain a person’s circadian rhythm [30] and, in sensitive individuals, lead to bipolar disorder [31]. It’s also interesting to note that one common treatment for bipolar disorder, lithium, is also one of the only known substances to directly affect a person’s circadian rhythm.

We are incredibly social animals – just think of how important the village, the tribe, the community, the family and language are to our identity as humans – and we are shaped by our interactions with others. It’s no surprise that social cues can have physiological effects on our circadian rhythms, too.

Temperature Cycles

Temperature cycles often correspond with light and dark cycles, but there is evidence that temperature acts independently on certain species’ circadian rhythms. Temperature cycles entrain the rhythms of drosophila [32], a type of small fly; of the leafcutter bee [33]; and of the circadian-mediated locomotion patterns in certain lizards [34]. Note, though, that these guys all share a common trait: they are not homeotherms [35]. They rely on exogenous sources to regulate their body temperature. Very few mammals, other than maybe the pocket mouse and a kind of heterothermic (exhibits partial self-regulation of body temperature) bat, show significant circadian response to external temperature cycles, probably because they are largely homeotherms with the ability to self-regulate body temperature, as well as the temperature of the SCN pacemaker. When you put an SCN in a Petri dish and expose it to temperature fluctuations, the neurons respond. Thus, the human SCN is shielded from ambient temperature fluctuations, but body temperature fluctuations (even those driven by the clock itself) may affect the clock. Human core temperature is related to our circadian rhythms, but the ambient, environmental temperature cycle to which we are subject does not seem to affect the rhythm.

Regardless – extreme heat does make it hard to get to sleep, and I’ve always preferred crisp, cool bedroom air, so temperature does matter. Just not so much to our master pacemakers.

Sound Cues

It turns out that sound cues play a potentially large role in human (and other species’) circadian cycles, but I’ll discuss that more thoroughly tomorrow.

So What Does This All Mean?

Photic input remains the primary determinant of human circadian rhythm. You keep artificial (especially blue) light usage to a minimum as you approach your bedtime, make sure to get some natural (or even artificial blue) light in the mornings, and you’ll have taken care of most of your sleep-related circadian rhythm concerns. Just keep in mind that non-photic input matters, too – perhaps not as much as light, and the effects in humans are still being tested – and playing around with the peripheral rhythms might give you an edge. Tinker, as I often suggest (or even thinker, a la the Healthcare Epistemocrat [36]), especially if you suspect your rhythm is off and you’re getting bad sleep. Otherwise, don’t get too haphazard with the hacking. Our circadian rhythms are pretty hardy, but it’s always smart to exercise caution when messing around with physiological systems our best and brightest are still figuring out.

The following hacks are worth testing:

  • Intense exercise right before bed may suppress melatonin and delay the phase cycle. If your find yourself restless and too alert after your late night workouts, try earlier workouts.
  • Conversely, if duty beckons and you need to be alert and awake one night, an extensive exercise session enjoyed right before normal bedtime should suppress melatonin and prevent sleepiness.
  • Eating also appears to suppress melatonin secretion, so if you’re having trouble sleeping consider eating earlier in the evening.

You’ll just have to find what works for you. The good news is that we are pretty darn adaptable, and fretting over workout or meal timing [37] (as long as we don’t run marathons before bed or eat entire meals at 3 AM) is probably tougher on us than simply allowing our circadian rhythms to respond, react, and adapt to all the various zeitgebers we’re faced with every day.

This is a pretty big topic and new research is still coming out. This post was meant to introduce you to the topic at large. Let me know if it’s something you’d like to see covered in more depth in the future.

Stay tuned for tomorrow’s post on sound cues and circadian rhythms. Grok on!


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[7] how blue light can affect our circadian rhythms: http://www.marksdailyapple.com/how-light-affects-our-sleep/

[8] exogenous: http://en.wikipedia.org/wiki/Exogeny

[9] SCN is said to synchronize them: http://www.forbes.com/2009/10/14/circadian-rhythm-math-technology-breakthroughs-brain.html

[10] in rodent models: http://ajpregu.physiology.org/cgi/content/full/285/1/R57

[11] evidence: http://www.jneurosci.org/cgi/content/abstract/30/5/1894

[12] mammal: http://www.genestocellsonline.org/cgi/content/abstract/9/9/857

[13] primate: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0P-484NVT1-7P&_user=10&_coverDate=05%2F31%2F1977&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1407543505&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=a936944b3a4a4aca21698de748c17e83

[14] C-peptide: http://en.wikipedia.org/wiki/C-peptide

[15] correlated with reductions in melatonin: http://www.ncbi.nlm.nih.gov/pubmed/18271676

[16] showed: http://www.ncbi.nlm.nih.gov/pubmed/19150931

[17] leptin: http://www.marksdailyapple.com../../leptin/

[18] phase shift your circadian rhythms: http://en.wikipedia.org/wiki/Phase_response_curve

[19] evidence: http://jp.physoc.org/cgi/reprint/33/3/225.pdf

[20] study: http://www.ncbi.nlm.nih.gov/pubmed/15031136

[21] another: http://www.ncbi.nlm.nih.gov/pubmed/8023928

[22] convert night workers onto a daytime sleep schedule: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0P-3YYTM2J-15&_user=10&_coverDate=12/31/1995&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1407579105&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=d4bbcb298077e5a603ffe79d735725c7

[23] study: http://ajpregu.physiology.org/cgi/content/abstract/284/3/R714

[24] studies: http://www.springerlink.com/content/c6645h3g2614hw92/

[25] developed a mutual synchronization of their internal clocks: http://www.jstor.org/pss/4599313

[26] honeybees: http://www3.interscience.wiley.com/journal/119483311/abstract

[27] beavers: http://www.springerlink.com/index/m124565628491858.pdf

[28] bats: http://www.springerlink.com/index/tm131452516t6711.pdf

[29] humans: http://www3.interscience.wiley.com/journal/114079050/abstract

[30] can entrain a person’s circadian rhythm: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VB8-4KM470R-1&_user=10&_coverDate=10%2F31%2F2006&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1407656532&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=911adf627a9a2b03797cd09dae0e5592

[31] lead to bipolar disorder: http://circadiana.blogspot.com/2005/08/bipolar-avoid-night-shift.html

[32] entrain the rhythms of drosophila: http://www.cell.com/neuron/retrieve/pii/S0896627309006382

[33] leafcutter bee: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2P-4865KS1-H7&_user=10&_coverDate=01/01/1971&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1406379974&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=509d7b066a310ae6d80bfafb583b04ed

[34] certain lizards: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B73GK-485956X-B&_user=10&_coverDate=09/30/1966&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1406382613&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=4b077952c40fc3aeaccaeb8f218679f0

[35] homeotherms: http://en.wikipedia.org/wiki/Warm-blooded

[36] Healthcare Epistemocrat: http://epistemocrat.blogspot.com/

[37] workout or meal timing: http://www.marksdailyapple.com/intermittent-fasting-skipping-meals-healthy/

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