Body Clocks: Timing Exercise for Sleep and Circadian Health

I’ve covered the topic of sleep many times — as it relates to cardiovascular health, metabolism, and even adaptations to exercise training. Conclusions are generally well…nothing new. Proper shut-eye is important — no — critical for every single living human and animal. Despite our predilection to avoid sleep, even viewing the need for sleep as a “weakness”, evolution has nonetheless conserved this aspect of biology. What seems like a “waste of time” is an essential biological process.

Essential, yet neglected. In particular, sleep has been discounted in the field of health and medicine. Nutrition, exercise, and medication (though not in that particular order) are usually the three main pillars of treatment for most conditions. Sleep (the “fourth pillar”) rarely enters the picture, despite the fact that without it, the other three pillars likely crumble or otherwise fail to produce the intended benefits.

Society is deprived of both sleep and health.

Another pressing issue other than a blatant lack of sleep is circadian misalignment. The circadian system is our internal “body clock” that governs myriad physiological processes across a ~24 hour sleep-wake cycle. One area in our brain, the super chiasmatic nucleus (SCN) — the so called “master clock” — is known to fine tune and integrate much of how our circadian system functions. This happens because it receives environmental cues that provide our body with anticipatory information: how to respond based on what time of day it is.

Misalignment occurs because our circadian system gets the wrong cues from our environment (also called zeitgebers; from the German for “time givers”). These cues — things like bright light at night, shift work (being awake at the wrong time of day), and eating around the clock — throw our system out of whack. Humans once received natural signals like the setting of the sun to tell our body it was time to sleep — melatonin production amps up to prepare for bed time and loll us off to sleep.

Enter 2019. Bright light, 24/7 snacking, and other zeitgebers are flowing in all the time, our clock is dysfunctional, confused.

Misalignment has its consequences. Studies show that people who engage in shift work — which involves working outside the “typical” 9–5 schedule and usually includes working evening/night shifts — have a greater prevalence of cancer, depression, cardiovascular disease, sleep problems, accidents, and metabolic disturbances.

Meta analysis of studies on the association of shift work with cardiovascular disease events. Area(s) to the right indicate a greater risk due to shift work. Source: http://www.sjweh.fi/show_abstract.php?abstract_id=3700

With such a large amount of people involved in necessary shift occupations and another chunk of the population misaligned due to environmental and social reasons (social jet lag, REAL jet lag, etc…) how to we go about re-entraining the rhythms of individuals and society to match our biological patterns in order to prevent the adverse health consequences of circadian misalignment?

Exercise as a “time giver”

Think about misalignment as a change in when your melatonin levels peak (to signal it’s time for sleep). Normally, melatonin levels will be low during the day/active period, then start to rise into the evening, and peak somewhere around midnight while you’re sleeping, only to fall again before you wake up.

A misaligned circadian rhythm means that melatonin levels may peak earlier or later than what is “normal” (this is called a phase advance or a phase delay). As a result, you’re not able to get to sleep when you normally should. Outside of melatonin, circadian rhythms for metabolism, glucose regulation, and brain function also exist and can be misaligned, leading to mayhem among all physiological systems

A “normal” circadian rhythm for melatonin. Source: http://ib.bioninja.com.au/standard-level/topic-6-human-physiology/66-hormones-homeostasis-and/melatonin.html

“Retraining” a rhythm means getting the clock back to normal. One way to do this is by artificially imposing zeitgebers on the body to signal a phase shift. Bright light has been traditionally used to phase shift circadian rhythms. Applied at night — bright light delays the rhythm. In the morning/early afternoon, shift advances occur.

Exercise is another known zeitgeber. Many studies have shown that exercise has the ability to re-entrain misaligned rhythms (in humans) back to a light-dark sleep-wake cycle and reduce the health risks that come with circadian rhythm misalignment. Exercise timed at a specific point in the day can shift the onset/offset of things like melatonin, thyroid stimulating hormone, and body temperature.

We know that exercise can be timed in accordance with sleep and other activities to yield benefits. For instance, performing morning exercise has been shown to augment the nighttime “dip” in blood pressure that occurs — a process essential for reducing the burden on our cardiovascular system and lowering CVD risk. Morning exercise also increased deep sleep and reduced the time taken to fall asleep (also called sleep onset latency). This suggests that exercise can be strategically used to enhance health and restorative processes during sleep.

A new study investigated precisely which time(s) of day may be optimal to result in potent circadian system phase shifts. The study used what are known as phase response curves (PRCs) for exercise — these measure how much the circadian rhythms shifts in response to a time cue such as exercise.

Participants (an impressive 101 of them) were placed in a lab setting for about 5 days, during which they were subjected to an “ultra-short” sleep-wake cycle of 60 minutes sleep followed by 30 minutes rest. This was used to essentially erase external “time of day” information and normalize for an internal circadian rhythm without external influences.

Then, participants exercised for 3 consecutive days for 1 hour total at just one time of day; 1 a.m, 4 a.m, 7 a.m, 10 a.m, 1 p.m, 4 p.m, 7 p.m, or 10 p.m. This was the exercise stimulus that would serve as the experimental “cue” for the circadian rhythm.

The main outcome was the urinary concentration of 6-Sulphatoxymelatonin (aMT6s), a breakdown product of the “sleep molecule” melatonin which would be plotted and used to indicate circadian rhythm and any shifts that occured throughout the study.

Exercise at 7 a.m as well as 1 & 4 p.m resulted in significant phase advances (i.e. earlier peaks) in the onset and duration of melatonin responses. This, compared to the phase delaying (i.e. later onset) of melatonin that occurred when participants exercised at either 7 or 10 p.m. Strike one for nighttime exercise.

Example time series for aMT6s in three study participants showing a phase advance after exercise at 7 a.m, delay after 7 p.m exercise, and increased duration of onset following 4 p.m exercise.

Exercise as (circadian) medicine?

The implications of these and other findings are probably more theoretical than practical (for now!) Using exercise to promote “chronobiological health” is a pleasing hypothesis — something many would prefer to treating sleep disorders with medications or trying to counteract that pathophysiological effects of circadian misalignment after it’s too late.

If there were a way to sleep better and improve your cardiorespiratory and muscular health all at the same time, wouldn’t you take advantage of it?

Will we begin to prescribe exercise at specific times of day, in specific individual “doses” as a way to coordinate internal circadian rhythms? Muscles too have circadian signalling mechanisms, which act as messengers to the higher-up systems, telling them to get back in line and “sync up” with the SCN and the 24 hour rhythms of the world.

As science continues to unravel the complex interactions between all of our bodily systems, it becomes increasingly difficult to separate the influence that physical activity, nutrition, and now sleep, have on human health and longevity.

References

Youngstedt SD, Elliott JA, Kripke DF. Human Circadian Phase-Response Curves for Exercise. J Physiol (Lond). 2019;

Torquati L, Mielke GI, Brown WJ, Kolbe-alexander T. Shift work and the risk of cardiovascular disease. A systematic review and meta-analysis including dose-response relationship. Scand J Work Environ Health. 2018;44(3):229–238.

Karlsson B, Knutsson A, Lindahl B. Is there an association between shift work and having a metabolic syndrome? Results from a population based study of 27 485 people. Occupational and Environmental Medicine. 2001;58:747–752.

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PhD candidate at the University of Florida — Science writing with a particular focus on exercise and nutrition interventions, aging, health, and disease.

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Brady Holmer

Brady Holmer

PhD candidate at the University of Florida — Science writing with a particular focus on exercise and nutrition interventions, aging, health, and disease.

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