Circadian Rhythm
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Intro to Circadian rhythm
Our body keeps time. The rhythms of our body roughly match that of the earth’s rotation. These rhythms are cycles the body follows within a 24 hour day and it repeats these rhythms day after day. The circadian system is a network of interacting neural and hormonal pathways that entails more than driving the sleep-wake cycle, they include hormonal activity, body temperature, digestion, and immune function. Every organ, even every cell, has its own daily timed circadian rhythms, certain proteins interact with cells in the body, instructing them to be more active or to slow down.
Liken circadian rhythm as being like your dog or cat that expects to get fed at a certain time every day and lets you know if the regular timing isn’t met. Just like your pet, your body gets out of sorts when certain events don’t happen when expected.
Being out of sync with one’s circadian rhythms (circadian arrythmia) has been associated with obesity, cardiovascular disease, diabetes, gastrointestinal problems, neurodegenerative disorders (including dementia), skin issues and more.
How circadian rhythm works
Light enters the eyes (even through closed eyelids during sleep), stimulating a signal in the back of the retina and down a nerve tract to the circadian clock in the brain.
Add Graphic - light to eye to brain “Light enters the eye (even through closed eyelids during sleep) stimulating a signal in the back of the retina and down a nerve track to the circadian clock in the brain Source: Circadian Rhythms and Circadian Clock https://www.cdc.gov/niosh/emres/longhourstraining/clock.html"
Circadian photoentrainment is the process by which the brain’s internal clock becomes synchronized with the daily external cycle of light and dark. This process is mediated by retinal ganglion cells (RGCs) which are a type of neuron located near the inner surface of the retina of the eye. RGCs are separate from rod and cone photoreceptors of the eyes. RGCs send signals to the region of the brain that houses the circadian pacemaker.
The body’s master clock is a structure called the suprachiasmatic nucleus (SCN). The SCN contains about 20,000 nerve cells and receives the input from the eyes.
As the eyes perceive the bright light of day or the darkness of night, the SCN tells the cells to act accordingly. Light is what keeps in sync (or disrupts) the circadian rhythm within a 24-hour day.
Chemicals in the brain adjust a number of factors in the body, such as:
- hunger
- temperature
- arousal and awakeness
- mood
The body’s circadian rhythms control the sleep-wake cycle. As darkness sets in, the body’s biological clock instructs the cells to slow down. A key driver of the body’s circadian rhythms is melatonin, the sleepiness hormone. When the evening becomes dark, the hormone melatonin starts to rise and allows sleep to occur. Melatonin peaks around 2–4 A.M. and then reduces by morning, when the hormone cortisol starts to be released, allowing for wakefulness.
But the circadian rhythms control more than sleepiness-wakefulness, and the end result directly affects our health.
Circadian Rhythm and APOE4
APOE4 is the ancestral gene. For the vast majority of time, all humans were ApoEε4/4 as were the primates we evolved from. The other two alleles, ε3 and ε2, arose recently in evolutionary terms. As the ancestral gene, it’s been suggested that ApoE4s are ill-adapted to modern lifestyle/diet. Without electrical light, high-speed travel, constant food availability and around the clock work-life schedules, our ancestors' were in circadian harmony with their environment. Our ancestors were active during daylight hours and resting/sleeping during the darkness of night. But modern lifestyle ignores this day/night harmony and instead is filled with artificial light, ingested stimulants, environmental irritants, late night snacking, around the clock work demands and added stress.
Chronic circadian misalignment is associated with an increased risk of metabolic syndrome, cardiovascular disease, neurological conditions, and cancer. ApoE4s are particularly concerned with shortened longevity, cardiovascular issues, and Alzheimer’s Disease.
With particular emphasis on Alzheimer’s Disease, numerous studies have shown that cognitive processing is gated over the circadian cycle and memory retrieval is disrupted when the organization of body clock timing is compromised thereby contributing to cognitive deficits.
Circadian dysfunction not only contributes, but is also a symptom in Alzheimer’s Disease. Individuals with Alzheimer’s Disease often confuse morning and evening with sleep disturbances. They also often act differently in the fading light of late afternoon or early evening a condition called sundowning, or sundown syndrome.
Add Graphic - self feeding loop “The self-reinforcing loop of disrupted circadian rhythm in Alzheimer’s Disease. Source: Circadian clocks, cognition, and Alzheimer’s disease: synaptic mechanisms, signaling effectors, and chronotherapeutics, (Kari R. Hoyt & Karl Obrietan, 7 May 2022) https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-022-00537-9?fbclid=IwAR11GYivCStCnfXIVqO1mQ-AOxy-2Ii_zCwaigjF2oXvUQ8MjEWHZJFYCyc"
Circadian Rhythm Disruptors
Some things that disrupt our circadian rhythms
Light, especially blue light exposure close to bedtime
Sunlight contains many shades of red, orange, yellow, green and blue light rays. Combined, the full spectrum of colored visible light rays creates what we call “white light” or sunlight.
Add GRAPHIC - light spectrum – vertical “The visible light spectrum extends from red light which has long wavelengths and energy to blue light which has short wavelengths and high energy. Source: Blue Light Facts: Is Blue Light Bad For Your Eyes? https://www.allaboutvision.com/cvs/blue-light.htm
The different colors have different energy and wavelengths. On one end of the visible light spectrum is red light which has long wavelengths and less energy. On the other end is blue light which has short wavelengths and high energy.
The sun is the main source of blue light and the reason why the sky is blue. But of late blue light exposure has increased with artificial sources: digital screens (TVs, computers, laptops, smart phones and tablets), electronic devices, and fluorescent, CFL (compact fluorescent light) and LED lighting. We are spending more time than ever before exposed to these devices and at close proximity which is concerning since our eyes aren’t designed to be good at blocking blue light. ADD GRAPHIC - Sources of blue light “Natural exposure to blue light diminishes as the sun sets, but with the introduction of electronic devices and artificial lighting, our exposure is often elongated affecting the sleep-wake cycle by delaying and decreasing melatonin secretion”
Light exposure affects sleep-wake cycle by delaying and decreasing melatonin secretion. Melatonin is called the sleepiness hormone but it’s more, it also is the body’s first line of defense against oxidative stress, boosts the body’s immune systems and controls the output of growth and sex hormones. Melatonin levels decline gradually over the life-span anyway, aggravating this decline with blue light exposure adds fuel to the fire.
The Centers for Disease Control and Prevention (CDC) notes that the circadian clock is most sensitive around 2 hours before a person’s usual bedtime. Exposure to bright or blue light at this time can shift the need to sleep later, resulting in a person to get sleepy and fall asleep later in the evening and wake up later in the morning, out of alignment with the body’s natural circadian rhythm.
Stress
As just addressed in the above section on light, melatonin release is an important signal for the body, telling it to slow down for rest and repair.
But stress can cause the body to release counteracting hormones, such as adrenaline and cortisol. These hormones raise the heart rate to circulate blood to vital organs and muscles more efficiently, preparing the body to take immediate action if necessary, a reaction known as the flight or flight response. Chronic feelings of stress can cause the nervous system to maintain a heightened state of arousal for extended periods and result in sleep deprivation. Insufficient sleep can then cause further stress.
ADD GRAPHIC - melatonin & cortisol cycling The photo receptors in our eyes tell hormones when to cycle during a 24 hour day. The top graph reflects the natural cycle of cortisol and melatonin release, but artificial light disrupts the natural sun/darkness cycle. We need both cortisol and melatonin, but as shown in the bottom illustration, light of any kind can suppress the secretion of melatonin leading to sleeplessness and overproduction of cortisol contributing to further stress and adrenal fatigue.
While melatonin is the hormone that tells the body to sleep, cortisol is the hormone that wakes us up. Melatonin and cortisol are in an opposite relationship; when melatonin is high, cortisol should be low and vice versa but when elevated, cortisol suppresses melatonin production. When either of these hormones get out of balance, our ability to sleep is affected.
Any type of stressor can raise cortisol levels including chemical, toxic, psychological and emotional stressors. Blood sugar problems, sleep disorders like sleep apnea, as well as chronic infections and allergies can also cause elevated levels. SEE STRESS
Chronic feelings of stress can cause the nervous system to maintain a heightened state of arousal for extended periods and result in sleep deprivation. Insufficient sleep can then cause further stress.
Additionally, these studies Flattening of circadian glucocorticoid oscillations drives acute hyperinsulinemia and adipocyte hypertrophy (Stefan Tholen et al, 2022) and The circadian clock mediates daily bursts of cell differentiation by periodically restricting cell-differentiation commitment ((Zhi-Bo Zhang et al, 8 Aug 2022) suggest that stress-induced circadian clock disruptions influence weight gain disrupting metabolic health which in turn further interferes with a good night’s sleep.
Caffeine late in the day
Caffeine is a stimulant, thereby potentially interfering with sleep. Caffeine can be found in coffee, certain teas, some soft drinks, energy drinks, cocoa beans/chocolate, even over-the-counter medications that contain caffeine, such as Excedrin.
Half-life is the amount of time it takes for a quantity of a substance to be reduced to half the original amount. The mean half-life of caffeine in plasma of healthy individuals is about 5 hours. So since an 8 ounce cup of coffee has 95 mg of caffeine, if you consume one cup of coffee, after 5 hours you’ll still have 47.5 mg of caffeine in your body. However, depending on the person, caffeine's elimination half-life may range between 1.5 and 9.5 hours [Source: Pharmacology of Caffeine Additionally, the other half of caffeine that you consume can last much longer than 5 hours. People with caffeine sensitivities might feel symptoms for several hours or even a few days after consumption.
The American Academy of Sleep Medicine recommends that you don’t consume caffeine at least six hours before bedtime. [Source: Sleep and caffeine
Chocolate
In addition to containing caffeine, albeit less than the levels found in drinks such as coffee or tea, chocolate also contains theobromine, a mild stimulant. Although the effects of theobromine are mild, some people are more sensitive than other and they last longer than caffeine. The compound has a half-life of 7.2 hours. [Source: Health Benefits of Methylxanthines in Cacao and Chocolate (Rafael Franco et al, 18 Oct 2013)
Sweets / too many carbohydrates
When consumed, sugar and carbohydrates produce high levels of glucose (blood sugar). In response to this, insulin is released by the pancreas. The primary function of the hormone cortisol is to balance the effect of insulin, so if insulin is chronically high, so is cortisol. That evening dessert not only spikes insulin but cortisol too. Cortisol levels should be trending down in the evening, so that late day insulin/cortisol spike makes it harder to fall asleep.
Prescription and over-the-counter drugs
Melatonin uses the same passageways as serotonin so if you are taking something that is blocking serotonin, it will block melatonin as well. Also, certain drugs can cause the depletion of melatonin, including: NSAIDS, antidepressants, betablockers and estrogen containing medications. As mentioned in the section on caffeine, some over-the-counter medications that contain caffeine, such as Excedrin.
Shift work
By its nature, working late shifts, split shifts, or throughout the night is disruptive to the body’s circadian rhythms. The effects appear to last after an person’s schedule has returned to working during the day.
According to David Earnest, professor in the Department of Neuroscience and Experimental Therapeutics at the Texas A&M University College of Medicine. “When our internal body clocks are synchronized properly, they coordinate all our biological processes to occur at the right time of day or night. When our body clocks are misaligned, whether through shift work or other disruptions, that provides for changes in physiology, biochemical processes and various behaviors.” His research also found that the health impacts of shift work persist over time. The sleep-wake cycles of subjects on shift work schedules never truly returned to normal, even after subsequent exposure to a regular schedule. [Source: Shift Work Has Long-Term Negative Health Consequences (Texas A&M University Health Science Center, 16 Aug 2022)
Trying to catch up on sleep over the weekend
Despite the thought a person can catch up on sleep, research has shown that it can take up to four days to recover from one hour of lost sleep and up to nine days to eliminate sleep debt. [Source: Estimating individual optimal sleep duration and potential sleep debt. Scientific reports (S Kitamura et al, 2016)
While sleeping in for a morning or two may help, it’s not enough. According to this study, Ad libitum Weekend Recovery Sleep Fails to Prevent Metabolic Dysregulation during a Repeating Pattern of Insufficient Sleep and Weekend Recovery Sleep (Christopher M. Depner et al, 18 Mar 2019) weekend recovery sleep failed to prevent later timing of energy intake, weight gain, or reduced insulin sensitivity during recurrent short sleep following the weekend.
Quoting David Earnest, professor in the Department of Neuroscience and Experimental Therapeutics at the Texas A&M University College of Medicine, “Even those of us who do work regular schedules have a tendency to stay up late on the weekends, producing what is known as ‘social jet lag,’ which similarly unwinds our body clocks so they no longer keep accurate time. All this can lead to the same effects on human health as shift work.” [Source: Shift Work Has Long-Term Negative Health Consequences (Texas A&M University Health Science Center, 16 Aug 2022) Additionally, each hour of social jet lag is associated with an 11% increase in heart disease risk, and social jet lag is also linked with fatigue, poor mood, and worsened overall health.
Travel
Flying through two or more time zones can upset your body’s established circadian rhythms. This is known as jet lag.
Late night eating
Our body’s insulin sensitivity follows a circadian rhythm. We are most insulin sensitive in the morning and insulin resistant at night. Late night evening go against our body’s natural rhythm leading to weight gain. Additionally, the muscles that digest food are working when they should be resting which can delay falling asleep and can prevent you from getting the deep sleep which is when the brain's glymphatic system to “cleans” itself of toxins.