Sleep and Cancer, Circadian Rhythms, and the Color Blue

It  is Saturday morning. You have no plans for the day – no work, no chores, no responsibility. You plan on sleeping in; however, as the sun gently begins to jut through your blinds, crawling along the floor, eventually covering your closed eyes, your body has a different plan for Saturday morning. As sensors within our eyes, known as intrinsically photosensitive retinal ganglion cells, slowly get bombarded with these beams of light from the sun, they begin to tell our brain that it is time to wake up.1 The slow increase in light that our eyes experience and the gradual increase in signal that our brain receives reduces our sleepiness, and the activity within our brain resembling sleep – like slow-eye movements – dissipates as we wake up naturally.2

Yet, your Saturday morning stands in direct opposition to your Monday morning. A screeching alarm clock wakes you at 6AM. Your bedroom lights come on, abruptly signaling to your brain to wake up. Production of sleepiness hormones like melatonin is inactivated. Alertness and stress hormones, like cortisol, are abruptly released. Your heart rate and body temperature quickly rise.3 It takes your brain nearly an hour to start functioning optimally, which inopportunely happens during your hectic drive to work, midway through a snow storm.

So, what does this have to do with sleep and cancer?

Sleep and Cancer – Modern Mimicking of Our Circadian Past

Much like our heart’s pacemaker, setting the optimal rhythm to pump blood to nourish our organs, our circadian clock sets the pace for our awake and sleep cycles. Our natural circadian rhythm controls our sleep, body temperature, immune system function, many hormones, alertness during the day, and physical and digestive activity. For millions of years, our ancestors were awoken by the sun’s bright and warming rays, and the effects of these rays of light are obvious. Just like our relaxing Saturday morning described above, even when our eyes are closed we sense the brightness and our skin feels the warmth. Waking up naturally to the sun is pleasurable. Waking up to an alarm clock is not.

Yet, the sun’s rays are acting on our bodies at a level far deeper than our senses can perceive. While we eventually visualize the tanning caused from the sun when melanin production is stimulated within the skin,  the internal physiologic change is much more difficult to quantify. For instance, the ultraviolet rays turn on a process within the skin that produces cancer-fighting vitamin D, a hormone that supports the immune system. Our visualization of light is no different as our eyes are bombarded with images from our world sent to our brain via the retina. Yet, much like the skin, a deeper change also occurs during this process.

When exposed to the sun’s blue rays, the retina sends a signal to a part of the brain called the suprachiasmatic nuclei (SCN). The SCN fires throughout the night, ordering the pineal gland to release melatonin. During the day, however, blue light from within the sun’s rays disarms the SCN. The pineal gland, historically known as the gateway to the soul, releases melatonin during nighttime as part of the circadian rhythm.4 Melatonin begins to signal to our body that it is time to sleep and repair the damage from the day, while fueling a number of our natural physiologic processes.5

The relationship between nature and the human body is never quite that simple. Far beyond inducing sleepiness, the release of melatonin results in dozens, if not hundreds of metabolic and physiologic changes as our body aims to remain in homeostasis—a healthy state that fixes and resists potential damaging changes. As melatonin circulates throughout the body, it scavenges cancer-provoking free radicals, thwarting their damage.6 Additionally, it inhibits several cellular pathways that can increase the risk of cancer.7 It supports the immune system to help fight inflammation, foreign invaders, and cancer. It also reduces the risk of breast cancer by offsetting excess estrogen stimulation8 (estrogen can fuel breast cancer cells) and may reduce our risk of dying from cancer.9,10

This is all, of course, if our body is functioning properly as it follows nature’s circadian pacemaker that has been implanted within our brains, setting our rhythm each day and night, as was occurring in our ancestors over the past millions of years. Even when we create artificial daylight cycles in scientific experiments, our sleep is dictated by the amount of light we encounter. Nature’s light cycles dictate our sleep and we have no choice but to follow her lead – when placed in an artificial “winter” with only 10 hours of daylight, we sleep significantly longer than an artificial “summer” with 16 hours of light. We also release significantly more melatonin during the winter-induced sleep.11 Our body follows nature’s lead as it sets our internal rhythm.

But what happens when this rhythm is broken?

Sleep and Cancer

Sleep and Cancer – Some Clues from Melatonin in the Blind

The use of cell phones, computer screens, televisions, and other light-emitting sources at night offset our circadian rhythm by shutting off our pineal gland, obstructing its secretion of the anti-cancer hormone melatonin. Counter to this artificial state are those individuals whose melatonin pathway is broken. Studies in blind individuals – those whose retinas do not send the blue light “off” signal – provide some important clues about the importance of melatonin.

In most cases, blind individuals who are unable to perceive light do not experience the inhibition of melatonin secretion like those of us with functional vision.12 When comparing totally blind individuals and those with severe visual impairment, scientists in Stockholm, Sweden found that the totally blind cohort experienced a 31% decrease in all cancers, a 33% decrease in cancers excluding breast and prostate, and a 31% decrease in cancers unrelated to smoking. The individuals with total visual impairment have nearly constant secretion of melatonin, even in the presence of light.13 No signal is able to pass from the retina to the brain in these individuals.

When I first heard of the decrease in cancer in blind individuals, I assumed it was from a less cancer-prone lifestyle. However, in this study, the fully blind or severely visually impaired led similar lives due to their legal blindness, yet experienced significantly different rates of cancer. Secondly, other data confirm this link, revealing an inverse association between visual impairment and breast cancer – i.e. the more “blind” a woman is, the lower her risk of breast cancer.14

Sleep and Cancer – Melatonin in Breast Cancer Patients

While melatonin may help reduce the risk of breast cancer, it also appears to be beneficial in women already diagnosed. Assessment of circadian rhythms and melatonin surges in women with breast cancer, benign breast disease, and age-matched controls reveal that women with breast cancer experienced half the amount of melatonin secretion during natural surges.15 While certainly not a smoking gun in implicating melatonin’s role in fighting breast cancer, perhaps more remarkable was the fact that melatonin secretion peaks during circadian rhythm and nocturnal concentrations of melatonin decreases as women’s tumor size and stage of breast cancer increases.16

Other studies have linked decreased urinary secretion of melatonin with breast cancer17 and decreased nighttime melatonin levels with estrogen sensitive breast cancer.15 The latter link is less surprising as low melatonin leads to an increase in serum estrogen (again, estrogen can stimulate breast cancer cells). Interestingly, Tamoxifen, the estrogen receptor blocking treatment for breast cancer may actually stimulate melatonin secretion.16

The decreased melatonin levels observed in breast cancer patients brings up a chicken or egg question as it is unclear if these women are at higher risk of breast cancer or if the cancer cells themselves have mechanisms to decrease melatonin as it serves as their adversary.

Damaging free radicals can wreak havoc on our cells and their genetic material, leading to irreparable damage, and eventually, cancer. Melatonin serves to protect these structures as it circulates throughout our body scavenging and disarming free radicals.18 Acting as our cellular bomb squad, melatonin directly offsets the damaging (oxidative) effect of these substances and serves to leave our body more resilient in its fight against free radicals by upregulating antioxidant enzymes like glutathione and superoxide dismutase. Melatonin also protects our cellular membranes from free radical damage, known as lipid peroxidation.19 Finally, melatonin appears to stimulate our immune system to help fight cancer and infections, though this direct relationship is less clear.20

Sleep and Cancer

Sleep and Cancer – Melatonin, Cancer, and Animal Studies

In science, hypotheses are often generated and first tested through animal and observational studies. The role of sleep and melatonin in health is no different, as animal studies assessing melatonin have been accumulating data for decades. For instance, when mice are exposed to DMBA, a cancer-causing chemical, 80% develop breast cancer. But if scientists first treat these mice with melatonin, only 20% of them develop cancer.21 Further linking sleep to cancer, if we remove the pineal gland in these mice – or in other words, remove their innate melatonin producer – cancer rates rise to 88%. Once the pineal gland is removed, melatonin supplements only minimally reduce the risk of cancer, further illustrating the importance of natural melatonin production.

In the petri dish, melatonin stops genetically altered breast cancer cell lines from rapidly increasing in number22 and suppresses the gene that allows these breast cancer cells to use estrogen as fuel.23 Melatonin even causes these cells to destroy their faulty parts to reduce the risk of cancer through a process called autophagy. Perhaps most concerning, simply altering light and darkness cycles in mice increases their risk of breast cancer.24

Sleep and Cancer – Lack of Sleep, Cancer, and the Health Risks

While observational studies in blind individuals reveal a decrease in cancer, studies in nightshift workers provide us with opposite findings. Working during the night directly interferes with our natural circadian rhythm by hijacking our normal melatonin secretion while disrupting a plethora of physiologic processes that normally occur at dusk.

Night shift work during only three nights per month is associated with a higher rate of cancer,25 with the risk increasing along with the amount of shiftwork.26 Shift workers seriously disrupt their circadian rhythm and secretion of melatonin and experience increased rates of anxiety, depression, chronic fatigue, colitis and ulcers, and cardiovascular disease.27 Working nights is also linked to an increase in the risk of colorectal cancer.28

Shifting gears back to mouse studies, when breast cancer-prone mice are subjected to weekly alternating natural light-dark cycles, they experience significantly higher rates of breast cancer.24 The researchers from this study also found that disrupted light cycles in these mice causes them to gain weight. Even jet lagging mice has been shown to lead to cancer from disruption of circadian rhythm.29

Sleep and Cancer – The Tangible Takeaways

We have studies showing that continuous melatonin production in the blind may significantly reduce the risk of cancer. Other studies show that women with breast cancer have significantly lower amounts of melatonin secretion than other women. Melatonin helps animals fight carcinogens to avoid cancer, and night shift workers, who directly interfere with nature’s circadian rhythm and melatonin production have significantly higher rates of cancer. Simply disrupting sleep patterns in mice increases their weight and cancer rate. The data are compelling, and healthy sleep patterns and circadian rhythms can help reduce the risk of cancer and improve our overall health.

How Long Should We Sleep to Beat Cancer?

To answer this question we turn to Japan, where breast cancer rates have risen from 28.3 per 100,000 people in 1991 to 39.5 per 100,000 in 2001.30 Assessment of nearly 24,000 Japanese women revealed that the more these women slept, the less they were diagnosed with breast cancer. The women were placed in groups of sleeping less than 6 hours, 7 hours, 8 hours, or greater than 9 hours. While this study merely observed women’s habits to draw conclusions, some serious statistical manipulation was undertaken to account for the differences between the groups. For example, those women that slept over 9 hours were generally older, ate less, and were less educated. While more sleep equaled less cancer, women who slept 6 hours or less had 1.6 times the risk of getting breast cancer. Were these women merely more stressed or not sleeping well due to health issues? We cannot answer this, but the data are consistent with our findings from above.

Crossing over into Europe, a study of 12,222 Finnish women echoed the findings from Japan. Women that that slept 9 hours experienced significantly lower rates of breast cancer than those who slept 7-8 and 6 hours.31 Data from Singapore linked less than 6 hours of sleep (versus 9 hours) with a significantly elevated risk of breast cancer.32 One of the few studies not showing a relationship between sleep and cancer was the infamous Nurses’ Health Study.33

Sleep necessity varies based on the individual, but eight hours seems like the magic number. I push for eight hours of sleep during the week and wake up naturally on the weekends which usually gets me between eight and nine hours per night.

Sleep and Cancer – Television, Computers, and Handheld Devices

While quantity of sleep is vital, quality of sleep may be just as important. Darkness fosters an environment that provides stimulus of our body’s natural production of melatonin. Blue light-emitting alarm clocks and television in the bedroom successfully deactivate our suprachiasmatic nucleus and its stimulation of the pineal gland. Blue light exposure at night has been shown to cause weight gain and impair metabolic function and glucose metabolism, increasing individuals’ blood sugar levels.34

Adolescents who use electronic devices are plagued by poorer sleep quality and difficulty falling asleep.35 To quote neuroscientist George Brainard (who I was lucky enough to be taught by in medical school):

“When you turn it off, it doesn’t mean that instantly the alerting effects go away. There’s an underlying biology that’s stimulated.”

Monitors and phones provide long-lasting physiologic effects as they alert the brain that it is still in the day cycle of the circadian rhythm and not yet time for sleep. Based on these findings, it is unsurprising that blue light and LED exposure at night decreases melatonin release in college students.36 Computer monitors resulted in less reduction than bright LED lights, which potently block melatonin production. Other results hint that even small amounts of light suppress melatonin, favoring a “lower is better” approach.37

Newer studies have shown that if we simply block the effect of blue light with orange-tinted lenses, our sleep may be safe. However, even with these changes, our eyes adjust to light at night, potentially disrupting our sleep. Scientists have shown that camping (in the Rocky Mountains no less) and placing individuals in situations that eliminates the possibility of excess light exposure after sundown resets our circadian rhythm for natural sleep and wakefulness cycles and optimal melatonin production.38 Sometimes simple solutions work best.

While the solution here is obvious – avoid light at night – this is clearly not feasible for everyone. My strategy is to avoid light as much as possible, and if I need to work at night, I use F.lux on my computer and Twilight on my phone. These apps automatically block out blue light when the sun sets. While I do not waste my time or money on cable TV, if I watch a movie, I connect my computer to the television to ensure blue light is blocked. I also use remote-controlled LED bulbs in my upstairs lamps from Limitless LED (take your pick as there are many brands). At night, I keep them set at a reddish hue and keep them blue in the morning.

Sleep and Cancer – More than Just Light

Different light sources have different effects on melatonin production.  As expected, bright light is worse than dim light.39Based on millions of years of the sun’s golden rays and blue sky leaving their imprint on our evolved physiology, the color of light works much like the notches of a key to open our brain’s circadian mechanisms. The blue of day blocks melatonin production, alerting to the brain that it is wake time, while red and orange light – much like the hue of a campfire – has a lesser effect on melatonin production.40 Those with light eyes may be even more sensitive to the effect of light on halting melatonin release.41

Other studies reveal that light is not the only nightly factor that can disarm the pineal gland. Even electric power and electromagnetic fields can disturb the circadian rhythm, reducing melatonin production.42 For instance, exposing the pineal gland to 60-Hz electrical fields halts melatonin production43 and simply applying a magnetic field decreases melatonin production in rat studies.44 These effects may be links to cancer, depression, and reproductive issues.45

Several population studies have confirmed the relationship between electrical fields and increased cancer risk, likely from melatonin disruption. Housewives from Oregon, residing in homes with electric heating, have a significantly higher risk of cancer,46 and women in households in Norway that are exposed to 50 Hz of electromagnetic fields have a 1.6 times higher risk of breast cancer.47 Even men apparently may have a higher risk of breast cancer, as shown in a study assessing New York Telephone workers with high magnetic field contact.48 Yet, electricians, power plant workers, and power line workers, with likely daytime exposure, still have six times the risk of breast cancer, revealing that there may be other factors at play as these exposures are likely happening during waking hours, questioning daytime pineal disruption.49

Finally, other studies point out that high levels of alcohol decrease melatonin secretion in animals and humans.50,51

The take-home message here is that the point of our bedroom is for sleep. It is unclear how important it is to have no wiring within the walls by the head of the bed, but most of us do not have the luxury of changing this. However, I keep my bedroom absent of clocks (especially with blue lights), televisions, and other electrical appliances that only serve to interfere with my sleep hygiene.

sleep and cancerWhile I don’t have any electrical appliances to disrupt my sleep, she does a pretty good job these days.

Sleep and Cancer – How to Maximize Circadian Rhythms and Sleep Health

Following society’s circadian template sounds easy enough, but what should we do when society requires a different path? In his book, The Story of the Human Body: Evolution, Health, and Disease, Daniel Lieberman describes “mismatch diseases” as basically sicknesses that surface from sidestepping the path to health dictated by nature due to societal demands. As poor sleep is associated with a plethora of diseases from obesity to cancer, Lieberman would certainly fit these into his category of “mismatch diseases.”

In today’s world, how can we placate both mother nature and modern society? Waking up naturally with the sunrise, going to bed when the sun sets, and avoiding all light and electricity at night sounds great, but what do those of us with jobs do? The intentional lifestyle sleep habits that have served me well are as follows:

Length of Sleep:

I get plenty of rest, including at least 8 hours during the week and 8-9 during the weekend. In worst case scenario, I get a minimum of 7 hours, though this rarely occurs.

No Electrical Devices in the Bedroom:

I turn off any computers or televisions an hour or more before bed. I generally try to read at night to avoid light stimulation. I use f.lux on all my computers and Twilight on my phone to block blue light emission from these devices.

Red Lights in the Bedroom:

I have absolutely no sources of blue or white lights in the bedroom. I use multicolored bulbs that can change with a remote control. I keep them red at night and blue during the day.

No Alarm Clock/Wake up Naturally:

There is no reason to know the time at night, which more often causes anxiety about the next day and interferes with optimal sleep. Waking up naturally with sunlight is refreshing on the weekends, but impossible during the week. I use a light that naturally brightens to simulate a sunrise, leaving the mornings as significantly less alarming than a buzzing sound. I set an alarm on my cellphone (on airplane mode) in the other room to make sure I wake up.

Exposure to Blue Light During the Day:

I work in the basement of the hospital, without windows or access to natural light. I make sure to get out for light exposure and a walk at lunch. However, I expose myself to blue light throughout the day by using a Phillips Blue Light Device. This tells my brain it is daytime, and has been shown to increase alertness, cognition, and thinking ability52 and reduce depression.53 Blue light has even been shown to outperform caffeine in stimulating cognitive function and alertness.54

No Cell Phone or Email at Night:

Besides the light-stimulating effects of checking email, the mental aftermath and anxiety that may follow is destined to interfere with optimal sleep. Even a one-sentence email from work can lead to anger, annoyance, and poorer sleep. Again – even though this simple act may take less than ten seconds, the reward is never there.

No Excessive Alcohol at Night:

I love my nightly glass of wine, but a large nightcap to help sleep or excessive alcohol will interfere with sleep. When the alcohol wears off, the sympathetic nervous system is activated, resulting in increased heart rate, less deep sleep, and potentially less melatonin secretion.

No Eating Before Bed:

Many fad diets tell us to not eat close to bedtime. This is good advice in most situations as eating and then lying flat can allow food and gastric acid to migrate upwards from the stomach to the esophagus, causing acid reflux.

Keep the Coffee in the Morning:

Studies show that caffeine can disrupt sleep and melatonin production.55 I enjoy a nice cup in the morning, but limit my consumption to the morning hours to reduce the chances of it interfering with my sleep.

Sleep and Cancer – In Summary

Sleep hygiene is vital for nurturing our circadian rhythm, supporting our optimal health, and fighting cancer. Maximizing our sleep/wake cycles will leave us feeling better rested, happier, and more productive. Shutting off our phone, computer, and television earlier in the night will leave us with more time to read, sleep, and enjoy life. This excess time will also allow us to go to bed earlier as the sun sets and wake up earlier when the sun rises, just as our ancestors did for millions of years.

Several small, but intentional steps can make a large difference in our overall health by maximizing sleep quality and allowing our natural cancer-fighting hormones to function optimally. Nature has supplied us with the machinery to achieve optimal health and fight cancer, and we must follow her lead.

Get to bed early, maximize sleep quality, wake up early with the sun, and sleep away cancer.