Circadian Misalignment - The Apeiron Life Perspective

9 min read

What it is:

Virtually every cell in the human body contains special timekeeping genes that dictate what happens and when by alternating windows of activity and rest. These circadian rhythms profoundly influence everything from mood and energy levels to how well food is digested, how effective medications work in the body at different times of day, and even disease risk.

These clocks tick at slightly different rates from cell to cell and person to person. Some people’s bodies do things earlier in the day and are inclined to reset more quickly, while others take their time. If placed in a sensory deprivation chamber, the body would “free run,” meaning that, over time, it would continue to have circadian rhythms, but they would become uncoupled from the solar day. Thankfully, environmental cues such as light, meal-timing, and physical activity synchronize us with the environment around us.

A master conductor in the brain plays an important role in this process. The suprachiasmatic nucleus (SCN) is a small cluster of neurons in the hypothalamus which receives input from the eyes about light levels in the environment. This serves as a time cue. Bright light in the morning tells the brain that it’s the start of the active phase and time to get moving. In contrast, the absence of light indicates the arrival of nightfall and time to rest. This rhythm is reinforced with other time cues, such as meal timing and exercise.

This system has evolved over millennia to allow us to optimize our place in the environment. Our night vision is poor, and we are inherently more vulnerable in the dark, so using the light to hunt, gather, and build makes more sense for our physiology. The system is primed for us to be active by day and resting by night.

The problem is that modern life presents many opportunities for our clocks to become desynchronized. This is termed circadian misalignment. If we don’t spend enough time outdoors or expose ourselves to too much light at night, the brain receives weak signals about where in the solar day we are and what our bodies should be doing. If we travel across multiple zones or have a fairly unstructured schedule, our bodies struggle to predict future behaviors. At the most extreme end of the spectrum, a nocturnal lifestyle such as in nightshift work creates an uncoupling of our behaviors from the biologically most appropriate times (e.g. eating during the night and sleeping during the day.) There is mounting evidence that this can create problems for our health and well-being.

The purported claims:

Circadian misalignment is associated with an increased risk of:

Cancer
Psychiatric disorders
Obesity
Type 2 diabetes
Cardiovascular disease

What the science says:

Cancer

In 2019, a group of scientists met at the International Agency for Research on Cancer (IARC) in France to finalize ongoing discussions about the potential association between nightshift work and cancer after numerous scientific findings had linked the two. Volume 124 of the IARC Monographs provides details of the evaluation. Using epidemiological and mechanistic evidence, they determined that shift work is “probably carcinogenic to humans.” Many major news outlets picked up this statement. The World Health Organization and Centers for Disease Control and Prevention both provide information about the dangers of nightshift work on their websites, including resources for those most at risk, such as nurses.

The relationship between shiftwork and cancer is complex. Most studies have looked at breast cancer and found positive associations. In studies where no association was seen, the scientists typically describe the many confounding factors that may have been responsible. Genetics and lifestyle clearly play important roles. A recent study found that a specific melatonin receptor gene polymorphism seemed to protect males against prostate cancer, which may be relevant for other types of cancer, including breast cancer. In other words, some people may have genes that make them more resilient to the negative impacts of being awake at night.

Melatonin is a potent antioxidant primarily released by the pineal gland in response to darkness. It is suppressed by light, and even though many nightshift workers use blackout blinds and eye masks when trying to sleep during the day, studies have shown that melatonin levels are generally much lower in these individuals. This suggests that not only is darkness important for healthy melatonin secretion, but specifically, darkness that occurs at the right time: during the biological night. Some people can adjust to night shifts and do recover their melatonin levels somewhat, but for most people, it will remain lower than it would be if they were sleeping at night.

A nightly dose of melatonin is essential for total body health. While it contributes positively to sleep onset and maintenance, melatonin is also a powerful antioxidant that mops up free radicals and prevents cell damage. This is important for keeping inflammation in check and protecting the body against cancer. Melatonin also lowers blood pressure and promotes the clearance of amyloid-beta, a peptide that is associated with the development of Alzheimer’s disease.

Many people are at risk of melatonin suppression, including those who work during the daytime. Bright light exposure at night via overhead lights or electronic devices can delay sleepiness. Combined with mandatory early morning alarms, sleep can be cut short from both sides.

Importantly, however, this is only one half of the coin. As well as avoiding artificial light at night, getting bright light exposure first thing in the morning is increasingly shown to be just as important for regulating circadian rhythms. Morning light starts the “daytime” clock and is accompanied by a boost in mood and alertness.

Mental Health

There is an established association between those with a later body clock (evening “chronotype”) and depressive symptoms. It has also been shown that those who experience chronic social jet lag may be at an increased risk of depression. An evening chronotype is also associated with bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder (ADHD).

Many factors give rise to these associations. Animal studies have shown that specific polymorphisms of circadian clock genes are associated with mania and other mood symptoms. But there are many ways that lifestyle may play a strong contributing role. A combination of too much time indoors during the day - particularly in the morning - and too much time in front of bright screens at night will naturally shift a person’s body clock later.

When pushed to the extreme, this desynchronizes a person’s internal clock from the clocks of peers and colleagues and can contribute to social isolation and loneliness. The latter is associated with worse health and shorter lifespan.

Cardiometabolic Health

There are other ways that a delayed sleep schedule can lead to mood disorders. A later sleep schedule is generally accompanied by later meal timing, and this is problematic because, in general, the human body is primed for consuming the bulk of calories earlier in the day when it is better able to process glucose.

A calorie is not just a calorie but has a different biological response depending on the time of day it is consumed. Some studies have shown that the time taken for cells to absorb glucose from food is much longer after meals consumed in the evening than those meals eaten in the morning. Eating when the body is not primed for handling the food can increase inflammation and contribute to cardiometabolic disorders such as insulin resistance and obesity.

It has also been shown that food intake can modulate circadian clock genes in many organs, such as the liver, which can alter the metabolism of fats and sugars. Meal timing also modulates the circadian rhythm of the gut microbiome. Meals eaten at night are associated with a pro-inflammatory gut microbiome that can increase gut permeability and dysfunction.

Shifting meal timing earlier can be a powerful way of moving circadian rhythms earlier and may promote better sleep at night. Eating meals within a window of about 10-12 hours during the daytime (called “time-restricted feeding”) may strengthen circadian rhythms and support better sleep, but also lower cardiovascular disease risk and systemic inflammation.

Weight loss interventions may be more effective and better maintained when coupled with earlier meal timing. In a study of 420 people who followed a 20-week weight loss intervention in Spain, those who consumed the bulk of their daily calories before 3pm experienced more rapid and dramatic weight loss than those who consumed the majority of calories after 3pm. In another study of 810 overweight or obese individuals who lost weight and had a two-year post-follow-up, those who reported better sleep were more likely to have kept off the weight.

Sleep

Getting adequate sleep leads to better next-day function, including mood and cognition. This protects against poor decisions regarding food intake. Well-slept individuals are less inclined to seek out highly palatable, unhealthier foods associated with weight gain and obesity.

Given that sleep, eating behavior, and physical activity are intrinsically linked, it is generally the case that improving one of these areas simultaneously enhances the others. Taking steps to minimize factors that impair sleep can be a good place to start. This includes minimizing the emotional stressors that can disturb sleep, sleep-disrupting substances, such as excessive caffeine, nicotine, long-work hours, and alcohol, which often eat into sleep time.

Poor sleep can perpetuate circadian misalignment due to subconscious changes at our metabolism level. Some of these factors can worsen sleep in a positive feedback cycle if left unchecked.

Healthy people generally experience a circadian rhythm in appetite. Ghrelin, the hunger hormone, typically peaks during the day and decreases at night. It has been shown, however, that ghrelin is often elevated the next day after a night of short sleep. This can combine with suppressed levels of leptin, the satiety hormone, to increase hunger and a stronger appetite. If this is paired with less physical activity, as a result of tiredness, this can drive weight gain. And given that weight gain is associated with worse sleep quality and even the development of sleep disorders such as obstructive sleep apnea, protecting sleep quality is essential.

Our take:

Modern life presents many opportunities for circadian misalignment that didn’t exist before the invention of electric lighting, globalization, and the “24/7” society in which we now find ourselves. While there is no denying that, in general, there has never been a better time to be alive in terms of scientific research, technological innovation, and global movement, there is also a never-ending stream of obligations vying for our time and attention. These can challenge our ability to unplug, relax, and truly rest.

Collaborating with colleagues on calls that span multiple time zones often requires at least one party member to forgo a regular sleep schedule or mealtime to get the work done. This contributes to circadian misalignment and, if left unchecked, some of the adverse health impacts discussed above. Frequent travel across multiple time zones also misaligns the body’s internal clock, and there is always a price to pay for this in terms of lost sleep or temporarily impaired cognition. Perhaps it’s a price worth paying for a couple weeks of vacation relaxation, but if we are always on the move, we may notice a negative impact over time.

There are other, subtler ways that circadian misalignment presents itself. Late nights on the weekend throw clock genes off course and may impair sleep when Monday morning rolls back around each week. For some people, this is accompanied by feelings of lethargy and trouble concentrating that can take a day or two to shake.

Perhaps more insidious, daylight savings time thieves millions of people of that crucial morning sunlight for six months out of the year, and this can lead to problems with mood, cardiometabolic function, and inflammation. Most people have a circadian clock that is slightly longer than 24 hours, and without the morning light “reset” that standard time provides, sleep time can shift later and promote tiredness the next day.

Will this benefit me?

Human physiology has not evolved to catch up with modern ways. Although we are still better suited to a natural environment, most of us spend our time balancing a busy “24/7” society. However, we can strive for balance by spending more time in nature and being mindful of nature’s daily and seasonal rhythms. Other practical tools include consistent sleep-wake timing, avoiding eating at night, and getting enough physical activity. Speak with your Apeiron Life Client Advocate to learn more about our jetlag protocol and how to minimize misaligning your circadian clock.

Still curious to try it? If you do, here's what to look out for:

Like any recommendations for optimizing health, it can be easy to worry about achieving perfection. The general rule of thumb is to strive for best practices about 80% of the time. Therefore, a buffer of 20% is available for unpredictable events such as late-night dinners with friends or travel. The good news is that protecting sleep and circadian health is one of the best ways of achieving longevity, preventing disease, and ensuring those experiences are possible for years to come.

References

Circadian Misalignment & Health - https://pubmed.ncbi.nlm.nih.gov/24892891/

IARC Volume 124 - https://publications.iarc.fr/593

CDC Nightshift - https://blogs.cdc.gov/niosh-science-blog/2021/04/27/nightshift-cancer/

Night shift breast cancer - https://pubmed.ncbi.nlm.nih.gov/31689664/

Night shift colorectal cancer - https://pubmed.ncbi.nlm.nih.gov/26208480/

Night shift prostate cancer - https://pubmed.ncbi.nlm.nih.gov/32872503/

Melatonin and prostate cancer - https://pubmed.ncbi.nlm.nih.gov/35064058/

Melatonin as an antioxidant - https://pubmed.ncbi.nlm.nih.gov/27500468/

Melatonin and Alzheimer’s - https://pubmed.ncbi.nlm.nih.gov/33254429/

Light at night and melatonin - https://pubmed.ncbi.nlm.nih.gov/30311830/

Light and circadian rhythms - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751071/