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Our modern lifestyle is disrupting a deeply ingrained, primordial, and universal code to being healthy.
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We also learned from this experiment that a daily eating–fasting cycle drives almost every rhythm in the liver.
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repeatedly disrupting your circadian clock can have adverse health consequences, as every system in your body starts to malfunction. It makes the immune system so weak that germs and bugs that don’t usually cause any trouble can upset your stomach or even cause flulike symptoms.
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the number one cause of death and work disability for active-duty firefighters is not fire or accident—it is heart disease, which is now thought to be linked to a disruption of the circadian rhythm.
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in 2007, the World Health Organization’s International Agency for Research on Cancer classified shift work as a potential carcinogen.19
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Scientists like me continue to examine the daily rhythms in adult human physiology, metabolism, even cognition, and we have found that almost every aspect of our daily life is rhythmic.
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Human growth hormone is also produced when we sleep.24 In fact, people who have insufficient sleep produce less growth hormone.
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At night, the brain also detoxifies. During the daytime, brain cells absorb and process nutrients, creating unwanted toxic by-products. These toxins are cleaned up when we sleep, and new brain cells are created through the process of neurogenesis.
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All influence of light on our clock goes through our eyes.
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In 2002, three independent research groups, including mine, discovered a light-sensing protein present outside the rod and cone cells that is, in fact, the light sensor that entrains the daily sleep-wake cycle to light.35,36,37,38 This light-sensing protein is called melanopsin.39 Of the 100,000 retinal neural cells that transfer all light information to the brain, only 5,000 contain melanopsin. Rod and cone cells can also entrain the circadian clock, but only in the absence of melanopsin, and when they do, they are not as efficient.
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When melanopsin is activated by registering blue light, it sends a signal to the brain that any light is present, and the brain responds by thinking it is daytime, regardless of what time it really is.
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Melanopsin has another peculiar property: It takes a lot of light to activate it. For example, if you open your eyes for a few seconds in a dimly lit room, your rod and cone cells can take in an image of the room, but your melanopsin cells will react as if it was too dark to see.
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This plant rhythm is synced to the rhythm of pollinating bees and insects that feed on the plants’ flowers.
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We learned that while circadian rhythms are influenced by light, the timing they follow is controlled internally, by genes.
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Now we know that inside every cell, the Per gene sends instructions to create a protein that builds up slowly and then breaks down every 24 hours. This is true for every organism: There are three genes that control the clock in pond scum, and more than a dozen in animals and humans.
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When he walked back into his darkroom lab, he noticed that the antennae, legs, wings, and abdomens that had been completely separated from the heads of the flies were still glowing in perfect rhythm, just like a whole fly would do. The organs did not have to be attached to the body to glow/dim with a 24-hour rhythm. This experiment proved that every organ in an animal has its own clock, and these clocks don’t need instructions from the brain in order to function. Plautz’s discovery was named a top-ten breakthrough of 1997 by Science magazine.
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Today we know that the clock in the gut times when to produce gut hormones for hunger or satiety, produce digestive juice to digest food, absorb nutrition, nudge the gut microbiome to do its job, and move waste out of the colon. The clock in the pancreas times when to produce more insulin and when to slow down.
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clocks in muscle, liver, and the fatty tissue we accumulate do the respective job to tune the organ’s function.
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What is more interesting is that the 20 percent of genes that are turned off for a specific time in the brain are not the same genes that are turned off in the liver or the heart or muscles.
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Now let’s take a look at what cellular activity occurs in a cyclic manner: The nutrient- or energy-sensing pathways—cell’s hunger and satiety pathways—are circadian. Just like our whole body feels hungry when it runs low on readily available energy and gets satiated after we eat, or does not feel too hungry at night, every cell in every organ has such a mechanism that makes the cell hungry and opens the door to let nutrients flow in during the day; and when the cell has enough energy, it closes the door so that it does not get overstuffed.
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The energy metabolism pathway is circadian, affecting cellular function and metabolism of all key nutrients. The use and storage of carbohydrates, fat, or protein is not a continuous process. When sugar is absorbed from the blood and converted to fat or glycogen for future use, the body’s fat-breakdown…
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Cellular maintenance mechanisms are circadian. Every chemical reaction, particularly when the cells make energy, produces a mess known as reactive oxygen species. This is similar to kitchen grease or the oily fume that comes off of a hot pan. To cope with those kitchen messes, we turn on the exhaust fan and put on a kitchen apron. Similarly, cells have a…
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Repair and cell division is circadian. Our body is being repaired and rejuvenated every day. Just like our plumbing gets weaker and leaks after a while, we have hundreds of miles of blood vessels that need to be checked for leakage and repaired. Similarly, our gut lining and skin needs daily repair to keep bacteria, chemicals, and toxins from entering our body. Inside every organ, many cells die and need to be replaced. Our blood cells also need replacement. This repair, through the production of…
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Cell communication is circadian. Our organs need to communicate with each other, and this happens within a distinct rhythm. For example, when we are full, the hormone leptin is produced in the body’s fat tissue, sending signals to the brain to stop us from eating more. Similarly, when we eat, hormones from our gut tell the pancreas to produce insulin so that glucose from our food is absorbed into our liver…
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Cell secretion is circadian. Each cell produces something of value for its neighbor or for the whole body. Consequently, every organ produces something that gets into the bloodstream or is delivered to its neighbor. The production and secretion of these molecules are circadian. For example, the liver produces several types of molecules that are necessary for forming blood clots. Since the blood-clotting factors are circadian, if we carefully measure our bleeding time or clotting time, we will see a clear circadian rhythm. This can optimize when we should schedule…
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Almost every drug target is circadian. This is one of the most relevant effects of circadian science, especially for people who are undergoing treatment for any chronic disease or cancer. Remember, thousands of genes in an organ turn on or off at a certain time. Imagine if you could target the gene that makes a protein that helps make cholesterol in your liver. That protein has a daily rhythm, making more cholesterol in the morning and less at night. If we want to reduce cholesterol…
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collectively known as the suprachiasmatic nucleus, or SCN, are strategically located at the hypothalamus, the center of the base of the brain, which houses the command centers for hunger, satiety, sleep, fluid balance, the stress response, and more. The 20,000 cells that make up the SCN are indirectly connected to the pituitary gland, which produces growth hormone; the adrenal glands, which release stress hormones; the thyroid gland, which produces thyroid hormones; and the gonads, which produce…
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in the very end stage of neurodegenerative diseases such as Alzheimer’s, if the SCN is also degenerated, the patient loses his or her sense of time: They go to bed or stay wide awake, feel very hungry, and go…
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The SCN is the link between light and timing, because it receives information about light from the outside world and shares it with the rest of the body. The melanopsin cells of the retina make direct connection with the SCN, which is why our master clock is most sensitive to blue light. When the SCN gets reset by light, it resets all the other clocks that are in the hypothalamus: the pituitary gland, adrenal gland, pineal gland, etc. The other clocks in the body, like the liver…
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The SCN clock is connected to the hunger center in the brain, so the SCN actually tells the brain when to feel hungry and when not to feel hungry. So, in that way, the SCN guides and instructs us when to eat, which indirectly instructs…
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There is a circadian rhythm for drinking water that helps our liver and muscles do many jobs. Liver cells swell up when you eat to make their own protein (liver produces most of our blood protein). The cells can swell only when they take up water. This is why we know that hydration helps organs do the…
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The clocks in different organs work like an orchestra to create three major rhythms that form the essential foundations of health—sleep, nutrition, and activity. What’s more, these rhythms are entirely interrelated and are also under our control. When they all work perfectly, we have ideal health. When one rhythm is thrown off, the others are ultimately upset, creating a downward spiral of poor health.
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As we age, the internal drive to have consolidated sleep or wakefulness slowly breaks down, and we wake up more easily when disturbed by light or sound and have difficulty getting back to sleep. This is when nurturing a body clock with better habits becomes critically important.
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Fu discovered another family who had a potentially different mutation in a gene called Dec2, which can reduce sleep need. People with this mutation can sleep for only 5 hours yet wake up feeling completely rested and can carry out their daily routine perfectly fine.7
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We saw that almost every liver gene that turns on and off within 24 hours completely tracked the food and ignored the timing of light exposure.9 That meant that it was the food that reset the liver clock, not the brain.
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Just like the first light of the morning resets our brain clock, the first bite of the day resets our organ clocks.
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But your circadian clock has many moving parts, and it is not that easy to speed all the clocks in different organs so quickly and get them back into alignment. Usually, they can adjust themselves by an hour per day.
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The same food that would have taken a couple of hours to digest at 6:00 p.m. takes longer to digest at 8:00 because you are outside of that optimal 10-hour window. This extra work interferes with the next task by delaying or even completely removing that task from the list.
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But when eating occurs at random times throughout the day and night, the fat-making process stays on all the time. At the same time, glucose created from digested carbohydrates floods our blood and the liver becomes inefficient in its ability to absorb glucose. If this continues for a few days, blood glucose continues to rise and reaches the danger zone of prediabetes or diabetes.
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These observations show us that when our rhythm is off and we come in contact with everyday bugs or viruses that we are typically resistant to, they can cause serious illness.
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one night of shift work can throw off your cognitive abilities for an entire week.
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For most people, our circadian clock takes almost 1 day to adjust to each hour of time-zone shifting; for some people, it can take 2 days per hour of time shift. Similarly, when you stay awake for 3 extra hours and delay your breakfast by 3 hours on the weekend, it affects your body in the same way as flying from Los Angeles to New York.
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One 2017 study showed that when sleep-deprived couples argue, they are more irrational or they perceive the other person as more irrational.
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If your work requires you to stay awake for at least 3 hours between 10:00 p.m. and 5:00 a.m. for more than 50 days a year (once a week), you are a shift worker and at risk of suffering from shift-work-related diseases.
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There are no right or wrong answers. However, if you answer “yes” to any of these questions, it is likely that optimizing your circadian system will benefit your health. Don’t worry if you aren’t perfect; almost everyone has room for improvement.
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(Download a PDF here) Assessing Your Responses
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answering three or more in each section is a sign that your circadian rhythms may not be optimal.
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Breakfast means “breaking the fast”: the time that passed the night before when you weren’t eating or drinking. But what constitutes a true break in a fast? The answer is whatever triggers the stomach, liver, muscles, brain, and rest of the body to think the fast has been broken. And that answer is anything you eat or drink besides water.
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(Download a PDF here) Assess Your Responses
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In fact, timing is the grand corrector for other behavioral habits. We have clinically seen that when people try to eat all their calories within 8, 10, or 12 hours, they also tap into the wisdom of our circadian body and brain.
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For every hour we stay awake, we later have to sleep 20 to 30 minutes. In the evening, the organs’ unique clocks synchronize with one another to create the perfect condition for sleep. The pineal gland inside the brain begins to produce the sleep hormone melatonin. At the same time, the heart clock instructs your heart rate to slow down, and the SCN instructs the body to cool down. Then, when the timing is right and the lights are low, you go to sleep.
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Sleep debt is the difference between the amount of sleep you should be getting and the amount you actually get. So, if you slept for 6½ hours last night, you’re beginning your day with 30 minutes of sleep debt. When you go to sleep the following night, you first repay this debt from the previous night. That means even if you sleep 7 hours the second night, it only counts as sleeping for 6½ again. That’s one of the reasons why we often sleep late on weekends: It’s the body’s way of repaying your entire debt.
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Napping Counts Toward Repaying Your Sleep Debt A short nap during the day is one way to repay your sleep debt. For example, if you had a sleep debt from the week of 2 hours and you take a Saturday afternoon nap, it’s possible to repay that debt in one nap.
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From tracking a million individuals, researchers have identified a pattern, known as the U curve of sleep and longevity.3 People who consistently sleep too little are more likely to die early than those who get the full 7 hours of sleep each night. Similarly, people who sleep as much as 10 to 11 hours are also likely to live shorter lives.
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The main culprits for insomnia are: Worry: increases the stress hormone cortisol, which is meant to keep us awake Too much food: keeps core body temperature too high for sleep Too little physical activity: reduces the production of the muscle hormone that promotes sleep Too much time spent in bright light in the evening: activates melanopsin and reduces melatonin production
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Spending the Day Outside Makes Nighttime Indoor Light More Tolerable When you spend a full day (4 to 5 hours) at the beach or at a park with bright daylight, you’re less sensitive to the effect of bright indoor lights at night.
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Pay attention to how much light you get during the day. If the only time you can recall seeing the sky is when you are driving to or from work, chances are you are not getting enough natural daylight.
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The main causes of fragmented sleep are: Dehydration Ambient temperature being too hot or cold Acid reflux caused by eating too late in the evening Sleeping with a pet Snoring/sleep apnea Other noise
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One study showed that children with attention deficit hyperactivity disorder (ADHD) have fewer symptoms when they have had enough sleep at night and exposure to light during the daytime.8 Adults with poor sleep habits are more likely to develop anxiety and depression, and seniors may experience memory impairment.9,10
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Sleep deprivation directly affects our hunger and satiety hormones, like ghrelin and leptin, both of which have a circadian nature. Ghrelin is produced in the stomach whenever the stomach is empty, and it is the signal to the brain to feel hunger. Leptin is produced in fat cells and signals the brain that you are full. However, poor sleep patterns disrupt these signals and make us more prone to overeat because the brain isn’t getting either of these two messages.
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Signs of a Chronic Sleep Problem Waking up with joint pain may be a sign that you did not get a good night’s sleep for several days in a row. Inflammation in the body is supposed to reduce during sleep. If you don’t sleep long enough, inflammation doesn’t have time to subside. You might find that if you sleep less than 6 hours a night for 3 or 4 nights, when you wake up your joints are stiff, or you might have a pain in your knee.
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But in controlled studies in Ken Wright’s sleep lab, participants who reduced their sleep from 8 hours to 5 hours consistently overate more calories than what would be required to fuel a few extra hours of wakefulness.
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Research in Mark Mattson’s lab at the National Institutes of Health has shown that mice that undergo a longer fasting period have better brain function, as keeping to a restricted eating time strengthens the connections or synapses between brain cells.13 A stronger connection between neurons means the brain can think better and remember better, regardless of how rested we are.
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In order to fall asleep, our core body temperature must cool down by almost 1°F.
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To have a good night’s sleep, we should have our last meal at least 2 to 4 hours before going to bed to ensure that the body is able to cool down.
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If you like a cocktail after dinner, a better habit would be to have your drinks before dinner, or during your dinner, provided it is 2 to 4 hours before bedtime.
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Sleep Is Inhibited by Light at Night The easiest sleep fix is to maintain a dark sleeping environment.
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Teens and Sleep Teens are especially susceptible to light and breaking the circadian code. Not only are they more likely to stay awake in the evening because of homework or their activities, there are also studies showing that teens are very sensitive to light.15 That means exposure to bright light in the evening delays their sleep and lowers their melatonin production. We can do at least two things to help our teens. First, we can prepare an early dinner in the evening so that they have an empty stomach before they go to sleep. They are most likely to fall asleep 3 to 4 hours after dinner. At the same time, we should also educate them by telling them about the importance of darkness and sleep. And perhaps we can establish a sleep-friendly environment for them to do their homework, including a table with a spotlight or lamp that illuminates the table but not their eyes.
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Taking melatonin after a meal slows down the decline in blood glucose to the normal level. Therefore, it is a bad idea to take melatonin right after eating: Wait for at least an hour or two after a meal so that the melatonin doesn’t interfere with your blood glucose level.
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In many individuals, natural melatonin levels begin to rise 2 to 4 hours before their most frequent bedtime. If this is true for you, the best time to take melatonin is 2 hours before bedtime. This means that if you are planning on going to bed around 10:00 p.m., take your dinner at 6:00 and your melatonin at 8:00.
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What’s more, over the first 12 weeks of the study, when the mice ate the same number of calories following the same high-fat/high-sugar diet that in 11,000 other publications had been shown to cause severe metabolic diseases, but within an 8-hour window, they were completely protected from the diseases normally seen with a poor diet. The time-restricted eating mice didn’t gain excess weight, and they had normal blood sugar and normal cholesterol levels. We believe that a shortened feeding period provides the digestive system the right amount of time to perform its function uninterrupted by a new influx of food, and enough time to repair and rejuvenate, supporting the growth of healthy bacteria in the gut.
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We found that 50 percent of all participants ate for 15 hours or more every day.
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The benefits of time-restricted eating (TRE) in humans is currently being replicated by other researchers.10,11,12,13
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Start by establishing a 12-hour window for a week or two, and then try to decrease the time you eat by an hour a week. The reason to do this is that the optimum eating window is between 8 and 11 hours. This is because the health benefits that you get from eating within a 12-hour window double at 11 hours, and double again at 10, and so on, until you reach an 8-hour window. Eating for 8 hours or less may be feasible for some, or for many of us over a few days, but it becomes difficult for many people to sustain this over months or years. While the science at 12 hours is impressive, lowering your window (to as few as 8 hours) is significantly advantageous.
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Time-restricted eating is never about counting calories; it is just about making you more disciplined about timing. We’ve found the best results for weight loss come with eating within an 8- or 9-hour window, and you can maintain this pattern until you get the desired results. Most of your body’s fat burning happens 6 to 8 hours after finishing your last meal and increases almost exponentially after a full 12 hours of fasting, making any amount of time fasting past 12 hours highly beneficial for weight loss. Once you’ve achieved your desired weight loss, you can go back to an 11- or 12-hour window and maintain that body weight. Of course, discuss your plans with your doctor before beginning any new eating program.
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This is important, as melatonin levels begin to rise 2 to 4 hours before your typical sleep time. Finishing your meals before melatonin begins to rise is necessary to escape the interfering effect of melatonin on blood sugar.
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Eating protein earlier in the day triggers the right amount of acid secretion in the stomach. So, instead of having more acid at night following a protein-rich dinner, you can switch to getting most of your protein in the morning and reduce your chance of getting heartburn and a poor night’s sleep.
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We do know that at night, melatonin level begins to rise to prepare our brain for sleep. Melatonin also seems to slow down our metabolism, and it acts on the pancreas, which produces insulin.
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When your melatonin level begins to rise in the evening and you eat, the food triggers the insulin response to begin. The insulin helps your liver and muscles absorb glucose from your blood so that your blood glucose doesn’t rise too high. But later at night, since insulin production is slowed down, there won’t be enough to soak up all the glucose from the food. This will leave your blood glucose levels high for a long period of time. At the same time, your body might store the excess sugar in the blood as fat instead of using it as fuel.
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(Download a PDF here)
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Is it possible to eat too much protein? Yes. The rule of thumb is your daily intake should be 0.36 grams of protein per day per pound of body weight. So, for someone who weighs around 150 pounds, that would be about 2 ounces of protein a day. Look carefully at this recommendation: Most of us are eating plenty of protein. However, too much protein (more than 1 gram per pound of body weight for several weeks or months) is not good for your health.
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Attention has a circadian component. We have an internal drive to be more attentive during the day and are naturally prone to being less attentive at night. However, sleep deprivation messes with your attention. A sleep-deprived brain cannot stay focused on tasks during the day, as the biggest distraction is feeling sleepy and dozing off.1
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Working memory is the most important function of the human brain; it separates us from all other animals. It involves the ability to absorb information, retain it, and connect it to information you have already learned.
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Sleep deprivation compromises your working memory by affecting your reaction time.
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Positive and negative reward assessments are how we use attention and working memory to make decisions.
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Positive and negative reward assessments also influence how we communicate. When we communicate with anyone, we have a good idea about what will make them happy and what will make them upset. Without good sleep, we’re likely to say something we’ll regret: In that way, sleep deprivation affects our relationships.
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The hippocampus is part of the brain’s most primitive area—the limbic system—and it plays an important role in the consolidation of information from short-term memory to long-term memory. Hippocampal memory involves calling up information you learned last week and applying it to the task at hand. One of the major functions of sleep is memory consolidation in the hippocampus.3 For instance, if you are learning a new language, starting a new math chapter, or playing a new video game, you are more likely to master the skill if you’ve had sufficient sleep than if you’ve had a few sleepless nights.
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Around 9:00 or 10:00 p.m., the alertness drive actually reverses: There is minimal drive to stay alert, and we go to sleep. That’s when your brain switches from active control to a default mode.
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Having less sleep disrupts a normal response to events and makes us susceptible to more extreme mood swings; we tend to be more irritable, anxious, and angry. What’s more, for most people, sleep deprivation tilts their mood toward a negative state.
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An animal study done at Johns Hopkins University showed insufficient light triggers depression-like mood and impairs learning in mice, and this effect was connected to insufficient activation of the blue light sensor, melanopsin.
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Your optimal brain function is highest between 10:00 a.m. and 3:00 p.m.; that’s when you should notice that your best work or learning is done. Studies have shown that this is the window during which we are in the right frame of mind for making good decisions, solving multifaceted problems, and navigating complicated social situations.
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From noon onward, your brain begins to slow down. This is a good reason not to lose an hour of top productivity by taking a long lunch. In fact, long lunches work in opposition to your circadian rhythm. If you work through lunchtime, or take a brief lunch break, I have found that productivity increases such that the same number of tasks that used to take 8 hours can be finished in 7.
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Let’s explore the three key components of sleep, light, and timing to see what you can do to optimize your circadian code and be more productive, given the realities of your life. My three biggest tips are: You have to give up the notion that staying up more hours will make you more productive. In fact, the opposite is true. If you set aside 8 hours for sleep opportunity (total time including sleep and preparation for sleep) to prepare for a productive day, you are giving your brain the rest it needs to be ready for the next day. During the day, optimize your productivity with natural light exposure to keep you more alert and productive. In the evening, adjust your light exposure to prepare your brain for restorative sleep.
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Daytime outdoor light is typically measured between 1,000 lux (a cloudy day) and 200,000 lux (full sun in a desert). An office without windows is typically between 80 and 100 lux; a home using overhead lights can be as low as 50 lux. The
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In modern times, an average person spends more than 87 percent of their time indoors; we average only 2½ hours outdoors,
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When you wake up, bright light is detected through the eye’s blue light sensor, melanopsin, and when that happens, melanopsin tells the brain to stop producing the sleep hormone melatonin and start increasing production of the stress hormone cortisol, which will help you begin to feel alert and ready to start the day. Bright light in the morning also synchronizes your brain clock to the daytime so that your circadian rhythm in learning and memory will begin to rise and you’ll reach optimal productivity a few hours later.
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Bright lights used during the day in the office or at home have been found to improve mood, alertness, and productivity.
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You need at least 1 hour of daylight exposure—being outside, driving in your car, sitting by a window where you can soak up at least 1,000 lux of light—to reduce sleepiness, synchronize your clock, perk up your mood, and stay happy and productive throughout the day.
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Whenever you are indoors, choose to sit right next to the largest window available. You might get 2,000 to 5,000 lux of light on a good day, but if you move 6 feet away from the window, the light may only be measured at 500 lux: a significant difference. And if your windows are covered by blinds or screens, your daytime indoor lighting may be 100 lux or less. Even the best, brightest LED light bulb only throws 1,000 lux.
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Studies have shown that both modest fasting and exercise have a similar brain-boosting effect. Each of them can increase a chemical called brain-derived neurotropic factor (BDNF) that improves the connection between brain cells and improves brain function.15,16
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Sleep loss leads to four major effects on our circadian code. First, lack of sufficient sleep doesn’t give our brain enough time to consolidate memories. Second, staying up late reduces brain function and productivity that night. Third, when we sleep less, we are exposed to additional light and the opportunity for eating in the middle of the night, both of which disrupt our circadian clock. Fourth, the following morning, as we wake up late and rush to work, we have little time to get the right amount of morning light exposure that will brighten our mood.
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A lot of scientific evidence supports the idea that high schools should start later in the morning.25,26,27 Delayed start times would positively affect students’ circadian code and would improve their alignment of all three factors: light, sleep, and food.
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adolescents are most sensitive to evening light, which delays their clock and bedtime. Their circadian clock does not wake them up early, yet schools are all scheduled to start early, sometimes before sunrise.
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Teachers then keep the rooms dark in order to use the overhead projectors. This is a dangerous trend because it further limits daylight exposure.
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Studies show that after exercise, the cells inside our muscles produce several molecules. One of them is interleukin-15 (IL-15), which was already known to increase bone mass. Interestingly, we now know that IL-15 also has some benefits on sleep. In one study, rabbits injected with a small amount of IL-15 were found to have better and deeper sleep.5
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A second mechanism occurs when muscle cells produce another molecule, irisin. Many obese people have less muscle mass and produce less irisin. Reduced amounts of irisin correlate with obstructive sleep apnea.6 Exercise for these people can reduce sleep apnea.
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Exercise in humans appears to increase the level of an enzyme that is involved in the production of heme—the pigment in our blood that carries oxygen to all tissues.9 The same pigment is also an important part of the circadian clock, as it tells the clock to turn on and off different genes involved in the metabolism of glucose and fat, as well as the production of hormonelike molecules from the muscle that can go through the bloodstream to affect function of the brain and other organs. This is one of the ways exercise can act on the muscle clock.
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we age or when our lifestyle is erratic, our circadian clock gets weaker. When this happens, the bone-making cells are not fully activated every day, so they don’t produce enough raw materials for making new bone. Similarly, the bone-eating cells are not fully activated, so they don’t clear all the damaged bone material completely. This ultimately leads to weaker bones that are prone to fracture. To maintain the healthiest bones, we need to have a strong sleep-wake cycle, eat at the right times, and exercise.
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Clock genes also determine the type of muscles we have. We typically have two types of muscles: Slow-twitch (type I) muscles are rich in mitochondria and help us perform endurance exercise or marathon running; fast-twitch (type II) muscles contain less mitochondria and help us when we are sprinting. Having a better clock appears to increase slow-twitch muscles.
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you exercise in a gym in the morning, don’t choose the darkest corner of the room. Instead, find a spot that is next to a large glass window or under bright light.
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Another great time for physical activity is at dusk or in the late afternoon,19 starting from 3:00 p.m. to dinnertime. This is when muscle tone begins to rise, so it’s the best time for strength training, including weight lifting, or vigorous exercise like intense indoor cycling. High-intensity athletes and those trying to optimize their physical fitness will find that exercising before dinner followed by a protein-rich meal will help them repair muscle, build muscle mass, and promote recovery.
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For average mortals (the majority of us), late-afternoon or evening exercise has two practical benefits. Exercise is known to reduce appetite,22 so afternoon exercise not only helps burn some calories, it can also help reduce hunger at dinnertime, so you may eat less. Exercise also helps our muscles take up more glucose in a mechanism that does not depend on insulin.23 As insulin production and release gradually decline through the evening, insulin alone may not be sufficient to prevent our blood glucose levels from shooting up beyond the healthy range. As little as 15 minutes of evening exercise will boost our muscles’ ability to absorb some blood glucose and keep it in healthy range.
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Now you’re pushing dinner out until 7:30, 8:00 p.m. That’s okay because exercise absolves some sins: The positive benefits of exercise outweigh a lost hour or two of TRE.
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National Toxicology Program evaluated the non–cancer related health problems related to light. They found that light exposure at night may be linked to heart disease, metabolic disease, reproductive issues, gastrointestinal disease, immunological disease, and a number of psychiatric diseases.
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If you don’t want to run out and buy a new television, add-on products can transform your current one. For example, Drift TV is a small box that connects to your television through an HDMI input and removes a percentage of blue light from the screen. You can set how much blue you want to take out: For example, you can set your Drift TV to remove 50 percent (or any percentage in increments of 10) of all blue light over a period of 1 hour. That way, the transition is seamless and virtually unnoticeable.
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What About Sunglasses? Sunglasses can reduce bright light reaching the eye by seven- to fifteenfold. That means if daylight inside a car is around 5,000 lux, sunglasses cut the exposure down to between 330 and 700 lux. Thinking about this math and knowing that my major source of daylight is when I drive to and from work immediately made me quit wearing sunglasses during my regular day’s activities.
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The digestive process is divided into stages, and each stage has a circadian component. The first stage, the cephalic phase, occurs in the mouth. Like Pavlov’s dogs, when we see food, think about food, or are accustomed to eating at a certain time, our mouth begins to produce saliva that is rich in enzymes, making it easier for the stomach to do its job. The mouth produces even more saliva as soon as we start chewing, while the brain instructs the stomach to release digestive acids. Nearly one-third of the acid needed for digestion is released in the cephalic stage. Even a small snack after dinner—a piece of chocolate, a glass of wine, even an apple—triggers the secretion of gastric acid, starting the entire digestion process, which then lasts for hours.
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Saliva secretion is circadian: It is most productive during the day, up to 10 times greater than it is when we sleep. The nighttime drop in saliva production helps us stay asleep, although it is another reason we wake up with dry mouth. Daytime saliva secretion neutralizes stomach acid that may come up through our esophagus into our mouth, but reduced saliva at night is not sufficient to carry out this task. Eating late at night can produce excess stomach acid, and if that acid comes back up the esophagus and into the mouth, there is not enough saliva to neutralize it.
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In fact, there is so much damage to our gut lining that 10 to 14 percent of cells are replaced every day. This repair and replenishment process is circadian. Every time we sleep, growth hormone secreted from the brain acts on the gut lining to repair itself, instructing the gut lining to check for damaged cells and replace leaky patches with new cells. The cells also secrete copious amounts of mucus to grease the gut lining, as some mucus gets depleted with every meal.
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Stomach acid production is typically high during the hours before bedtime, roughly 8:00 to 10:00 p.m.1 If morning stomach acid is produced at an arbitrary unit of 1, at night it reaches 5. However, when food is consumed during the day, your stomach acid production may go up to 50; eating the same amount at night may increase production up to 100. This means if we eat a modest meal in the evening, the stomach will produce a larger amount of acid than if the food was consumed at noon. This may be a defense mechanism of the gut to make sure that if a bacteria or pathogen were to somehow make its way to the stomach at night, the acidity of the stomach could destroy it before it got to the next phase, the intestinal phase, which slows down at night.
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Excess acid produced in response to a late-night meal fills up the stomach, and as food moves slowly along the digestive tract at night, this acid slowly creeps up and can come up to the mouth, causing acid reflux.
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This movement from intestines to elimination has a circadian rhythm: It is more active during the day, while at night the movement is very slow. This is why we don’t typically wake up in the middle of the night to have a bowel movement. Eating a heavy meal and lying down immediately afterward does not allow food to move down the intestinal tract as fast as it should, and this also leads to acid reflux.
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Instead of lying down and watching TV or other screens after dinner, a better habit to adopt is taking a short walk or doing some chores that require standing. Working with gravity, rather than against it, helps prevent reflux.
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Dietary fats are the most difficult to absorb. They require bile, produced in the liver and stored in the gallbladder, to convert them into an emulsion, which is later taken up in the small intestine and then in the bloodstream. Production of bile is strongly circadian. This rhythm not only makes sure that sufficient bile is ready to absorb fat from our diet, it also breaks down cholesterol in the liver. The absorption of glucose, amino acids, and fat is strongly circadian. Nutrient absorption requires a lot of energy, which is why it can’t happen all the time. Gut cells that absorb these nutrients and other chemicals in food have different channels or doors that allow only certain types of molecules to go through, and the opening and closing of these doors is circadian.
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During digestion, each macronutrient also activates different gut hormones. Amino acids (from proteins) activate the hormone gastrin that instructs stomach cells to release acid. Similarly, fat activates the cholecystokinin (CCK) hormone in the intestine, which in turn releases bile from the gallbladder. Many of the hormones and chemicals produced in the gut stimulate the brain to affect our emotions and cognition. For instance, CCK and other hormones produced in the gut affect whether we feel depressed, excited, anxious, or panicky.
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Sleep reduces the production of ghrelin so that there is less chance of us waking up and needing to eat. But when we don’t get enough sleep, even if our stomach is still digesting our last meal, our ghrelin level goes up and makes us think we are hungry.
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We believe that a sleep-deprived individual or someone who goes to bed late is more likely to eat late, which triggers CCK production. If there is a defect in CCK breakdown and CCK-4 accumulates in the blood, this might explain the increased incidences of anxiety in sleep-deprived people.
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She found that the gut clock was the slowest to reset to the new time zone.
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Eating at the time appropriate to the new time zone is the best way to reset the gut clock.
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After a few weeks of following a 10-hour TRE, Simon noticed a marked reduction in his general anxiety and panic attacks.
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There are some species of microbes that flourish under fasting, while others flourish during feeding. Therefore, the composition of the gut microbiome changes between day and night. In other words, we go to bed at night with one set of bacteria in our stomach and wake up with a different set, and in the middle of the day a different set appears.
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For example, when fecal matter from jet-lagged people is placed in the gut of healthy mice, the mice become obese. But fecal matter from healthy people, who have not traveled or are not doing shift work, does not trigger obesity in rodents.
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We gave them a high-fat/high-carb diet but kept them to a strict feeding-fasting cycle, and the mice remained healthy.9 Under TRE, one set of bacteria flourishes when mice eat, while a different set populates the gut during fasting.
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The gut microbiome under TRE changes the breakdown and absorption of fiber in a way that a good chunk of the sugars are not absorbed but leave the body during elimination. TRE also changes the gut microbiome in a way that converts bile acids into a different form that is excreted in stool. Since bile acids are produced from cholesterol, the more bile acid that leaves the body, the greater the reduction in cholesterol in the blood.
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For instance, the gut microbiome is now increasingly recognized as a contributing factor in autism. 11,12
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Preservatives are added to food to inhibit the growth of bacteria that spoil food. When these preservatives get into our intestines, even at a low concentration, they inhibit the growth of gut bacteria, affecting the composition of the gut microbiome. Some food preservatives, such as carboxymethylcellulose and polysorbate 80 (an emulsifier used to make foods like ice cream smoother and easier to handle, as well as to increase resistance to melting), also have detergent-like properties that inhibit bacterial growth by thinning the protective coating around bacteria cells. However, our gut mucosa has a similar coating. Food preservatives can corrode the protective mucosal lining that separates microbes from the cells that line the gut. When these unwanted microbes make contact with the cells in the gut lining, it can cause inflammation, such as colitis.13,14 TRE promotes repair of the gut lining and may counteract the negative effects of a bad diet.
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Just one day of eating late at night may leave you with a bad feeling in your stomach the next morning. If it continues for a few days, acid reflux may increase, and your gut may not have enough time to repair all the damaged cells in the gut wall. If random eating continues for many weeks, acid reflux and heartburn (known as gastroesophageal reflux disease, or GERD) may become a permanent fixture in your life.
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The drugs that belong to the class are called proton pump inhibitors (PPIs); having more protons in the stomach means more acidity, so PPIs essentially inhibit molecules that pump more protons into the stomach. As you can imagine, these drugs change the pH of the stomach and make it less acidic. But the body fights back and tries to make more acids or more of the hormone gastrin, which tells the stomach to make more acids. This may lead to dose escalation. Once one uses PPIs regularly for a few weeks or months, the gut chemistry also changes in such a way that the person becomes dependent—even addicted—to PPIs.
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As stomach acid reduces, more bacteria can survive in the stomach and enter the small intestine—some of which can be pathogenic. This is how PPIs can lead to infections and diarrhea.
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200,000 patients in the United States, regular PPI use was found to increase the chance of acute kidney disease or acute inflammation of the kidney by threefold.20,21 The adverse effects of PPIs extend even to the brain. There are some studies that show chronic PPI users may have an increased risk for dementia. PPIs are also used for the prevention of a host of other diseases, including stress ulcers, peptic ulcer disease, gastrointestinal bleeding, and H. pylori.22
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Continuous use of these drugs is also linked to changes in bone density, causing osteoporosis and bone fractures.
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our body begin to start burning some fat. This is the critically important aspect of TRE: to stop feeding the engine that is your body and let it run on the fuel it already has. This is the only way to prevent or reverse weight gain and, ultimately, obesity.
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When the adipose cells reach their full capacity, our body tends to store fat in cells or organs that are not designed to store it. This compromises the function of organs such as the liver, muscles, and pancreas. When there is excess fat in cells, there is less space for the cells to carry out their normal tasks of generating energy. This factor is linked to a range of diseases from fatty liver disease to diabetes, heart disease, high blood pressure, and even cancer.1
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When cells carry excess body fat, there is also less space for the endoplasmic reticulum (ER), the canal system within a cell that connects to the cell membrane and then to the outside of the cell. Cells always secrete something through this canal during the daily repair cycle. But when the ER is stressed, the cell’s overall repair process is hampered. Some body fat is also converted to the type of fat that causes inflammation and is released into the blood. These inflammatory fats can contribute to inflammation all over the body.
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In the morning, blood glucose levels stay within the safe zone. As the day progresses, the same meal causes your blood glucose levels to rise higher and stay high for a longer period of time.
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We found another interesting connection between cholesterol and fat. TRE increases the level of an enzyme that breaks down cholesterol in the liver. Cholesterol is usually broken down into bile acids. TRE mice showed a reduction in their blood cholesterol to normal levels and a slight increase in bile acids. A small increase in bile acids is considered good as it triggers a program in fat cells to burn off fat.10
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We also know that systemic inflammation subsides with TRE.11 Systemic inflammation is the mother of many metabolic diseases: diabetes, fatty liver disease, atherosclerosis, and others.
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instance, the most widely used drug to fight diabetes is metformin, which works by activating a protein called AMP-activated protein kinase (AMPK), which triggers better control of glucose and fat metabolism. Interestingly, TRE mimics the effect of metformin by increasing fat burning during the fasting stage.
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Many cholesterol-lowering drugs, known as statins, act on the enzyme that mediates the first step in making cholesterol. The same control point is also clock regulated. Under TRE, the rhythm in this enzyme improves; it naturally turns off for half of the day, which essentially mimics how statins work. Statins have adverse side effects, including muscle weakness and muscle pain. Edie, a patient who had been on statins for many years and always had muscle pain, almost completely got rid of her muscle pain after adopting a 10-hour TRE, and she had an easier time with her medication.
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In a study of 596 patients who underwent either morning or afternoon aortic valve replacement, during the 500 days following surgery, the incidence of major adverse cardiac events was lower for those people in the afternoon surgery group than in the morning group.13 The differences in circadian rhythms in gene expression over the course of a day may cause a person’s heart to heal more quickly in the afternoon than in the morning. These first few hours of healing strongly determine the outcome and long-term recovery, which is why you want your healing to coincide with your circadian rhythm.
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However, just like the major organs, the immune system has a circadian component, and if you can resync it, you can regulate its response. What’s more, disrupting your circadian code affects your immune system, making you more susceptible to diseases or infections and making it more difficult to recover quickly. For instance, wound healing has a strong circadian component. Both bleeding and clotting time have to be exquisitely balanced: You don’t want to clot too quickly. A blood clot is like a cement patch on a leak. The bonding structure is made of proteins produced in the liver, which we know is strongly circadian. If we bleed for too long before the clot forms, we can develop an infection.
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Shift workers have been shown to have fragile immune systems. Compared with non–shift workers, shift workers have a higher incidence of the inflammatory diseases of the gut (colitis), as well as higher risks for developing bacterial infections, several types of cancers, and many other immune system–related chronic diseases, including cardiovascular disease and arthritis.
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The clock genes play an important role in deciding how much of each type of immune cell our body should produce. When our clock system breaks down, it causes a cellular imbalance to our immune systems, producing more of one type of defense at the cost of another.
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Oxidative stress has been shown to be an important factor in many diseases because it leads to chronic and systemic inflammation. In fact, the number one biological mechanism that seems to underlie most chronic disease states is oxidative stress, and the results can include cancer, heart disease, dementia, arthritis, muscle damage, infection, and accelerated aging. One of the central roles of the circadian clock is to control oxidative stress. After eating, when every cell in our body uses nutrition to make energy, cells produce reactive oxygen species. The clock acts as a sensor of this oxidative state inside the cell and coordinates antioxidant defense mechanisms to clean up the damage. Since eating used to happen predictably during the daytime for millions of years, this function of the clock is very fundamental to cellular health. Scientists believe this predictable rise and fall of oxidative stress between day and night might have been one of the primary instigators of the evolution of the circadian clock.2
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Autophagy is more active several hours after our last meal (after several hours of fasting and before the first bite of the day), and then slows down when we eat. Time-restricted eating is known to increase autophagy for a few hours during the fasting period.3
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healthy circadian rhythm improves mitochondrial function, mitochondrial repair, and autophagy, which in turn improves overall cellular health.
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We have found that when we disrupt the circadian code in mice, every cell behaves as if it is under attack.5
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Each immune system’s distinct tasks—surveillance, attack, repair, and cleanup—occur on a schedule and at different times of the day. This may seem counterintuitive, because you might think that all immune responses should be happening at the same time: when the threat is detected.
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This rhythm in immune function also serves as a check against chronic inflammation. In other words, the loss of circadian regulation of the immune system might be another cause of chronic inflammation.
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Circadian disruption also makes the tissue of brain cells stressed, and the stressed cells produce many chemicals that activate these tissue immune cells, leading to chronic inflammation.
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Inflammation of fat deposits is a general feature of obesity. This further compromises the fat cells’ normal function to burn fat when needed. When the liver is damaged due to excessive fat deposits, it produces chemicals that invite immune cells to try to repair it. This leads to the liver filling up with scar tissue, also called steatohepatitis or in extreme cases liver cirrhosis.
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ICU delirium can happen to anyone in a hospital room, given sleep deprivation and the lack of any sense of time or light. It’s possible that ICU delirium occurs when the immune system is compromised, but we believe that it has more to do with a circadian disruption. When people are in the hospital, they are poked every 2 to 3 hours, they don’t have continuous sleep, the lights are on all the time, and they are often attached to an IV line, which means food and medications are provided at random times or constantly.
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So, taking any anti-inflammatory drug before bed can preemptively reduce the severity of nighttime inflammation, and you may wake up with less arthritis pain in the morning.
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Plan your vaccination day in advance, and try to get a week’s worth of good sleep beforehand. In one study, when participants had poor sleep for a few days before vaccination, nearly half of them showed significantly delayed response to the vaccine.13 This
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In 2007, the World Health Organization’s International Agency for Research on Cancer declared shift work that involved circadian disruption to be a “probable” carcinogen.
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Cancer has many different causes, and some have a circadian component: Excessive inflammation: As we discussed, inflammation is circadian, and when chronic inflammation continues, particularly in the gut or liver, it contributes to cancer growth. Free radical oxidative stress: Free radicals can damage cellular DNA, and with the damaged DNA there are mutations, some of which can be cancerous. Telomeres: As the circadian clock is involved in DNA repair, it also has some effect on maintaining healthy telomeres (the ends of chromosomes). In one study, women who worked the night shift for 5 years or more had reduced telomere length and an associated increased risk for breast cancer.17 Immune system surveillance: Some immune cells are on the lookout for tissue that doesn’t look right, and when they find it, they kill it. This is a very clear example of productive autoimmunity because when the immune system finds a cancer cell that’s 90 percent like a normal cell, it kills it. When this immune system is compromised, as happens under circadian disruption, many cancer cells escape a weak surveillance and grow to become life-threatening tumors. Cell cycle checkpoints: One of the fundamental differences between a normal cell and a cancer cell is that normal cells don’t grow quickly nor do they divide that often, while cancer cells grow much faster and divide more often. When normal cells divide, they need to be in perfect form. The circadian clock in a normal cell makes sure that many control steps are in place for the cell to grow only at certain times, divide only once a day or every few days, and repair itself more regularly. Cancer cells escape all of these checks and balances. They grow much faster by escaping the circadian mechanism that rations nutrients for the cells. Cancer cells make more fat molecules that build new cells and they recycle their waste product to fuel their rapid growth. Cancer cells also don’t have a stringent DNA damage repair mechanism, so they slowly accumulate DNA damage. Metabolism: Cells require a lot of energy when they are growing. The circadian clock controls metabolism, but when the clock is broken, metabolism speeds up, and that fuels cancer. DNA damage response: If DNA is damaged, it has to be repaired, and the circadian clock regulates some of the repair enzymes so that the repair system is on when the cells are likely to get damaged. For example, in the gut, the DNA repair system is on in the middle of the night. The skin’s repair system is timed for the late evening so that it doesn’t compete with daytime damage from the sun. If the timing for repair is off, the cell may divide into new cells before its damaged DNA is repaired. A proliferation of damaged DNA increases one’s chance of developing cancer. Autophagy: Cancer cells use autophagy to fuel themselves. As soon as something is damaged, they immediately take it and recycle it. As we learned, autophagy is regulated by a clock, so it occurs only at certain times…
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found that women who maintain a regular eating schedule and an 11-hour TRE are significantly protected from breast cancer.18 Since TRE is known to reduce chronic inflammation—which is a recipe for cancer—it makes sense that TRE for
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They found that tumors grew more aggressively in mice under shift-work/jet-lag conditions.
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This was the first study that showed that mistiming a drug led to worsened side effects. The study was reviewed in an article provocatively titled, “Dosing-Time Makes the Poison: Circadian Regulation and Pharmacotherapy.”22
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A circadian clock is present in almost all brain regions, including the areas that are implicated in neuropsychiatric diseases. Although we do not completely understand how brain dysfunction starts or develops, the mechanisms of these diseases primarily involve four themes, and the circadian clock is involved in all of them:
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The circadian clock regulates several aspects of adult neurogenesis. There is a daily pattern to the process of stem cells giving rise to new neurons, making sure that the right type of healthy fat molecules is delivered to the new neurons at the right time of the day. When we boost our circadian rhythm, more healthy neurons are created. Conversely, when we do not have enough sleep or when we experience jet lag, we reduce the number of new neurons that can be made that day.
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An imbalance in the right amount of light (too little light during the day or too much at night) or an irregular sleep-wake cycle may leave a lasting impact in the form of a permanent change in sleep pattern, hypersensitivity to light, or even conditions like autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD). In mice, melanopsin cells from the retina that are miswired to the brain can result in light-induced headache and migraine pain.2 The same may be true in people when they spend too much time under bright light.
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The circadian clock regulates the genes that are involved in reducing neuronal stress, promoting their repair so that neurons remain healthy.
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Some brain clocks are involved in making these brain chemicals, while others are involved in breaking down the chemical production cycle. When the clock is disrupted, the daily rhythm of brain chemical production becomes mistimed or is stuck at high or low levels. This is when we develop different brain diseases. For example, when mice don’t have a clock in their brain, they produce too much dopamine—a neurotransmitter related to energy use in the body, metabolism, and activity.3 Too much dopamine makes both mice and men manic.
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where the timing of light is advanced or delayed by as little as 1 hour each day for only a few weeks, their circadian clock completely rewires for the rest of the mouse’s life.7,8 We believe this effect is entirely due to how the master brain clock in the suprachiasmatic nucleus (SCN) reprograms itself by turning on or off a unique set of genes. This research is groundbreaking
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The altered lighting schedule affected the production of the neurochemical GABA, which is known to keep us calm. Interestingly, the majority of SCN clock neurons produce GABA, and we also know that having too much or too little GABA has a huge impact on our daily organization of the sleep-wake cycle, as well as our ability to stay calm or become anxious.
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In a newly discovered phenomenon, there seems to be a special drainage system in the brain, called the brain lymphatic system. This system operates during sleep to remove the metabolic waste of the brain. Sleep increases this process by as much as 60 percent.12 So, whatever good habits you may have during the day, having a good night’s sleep is the best way to remove all the waste products from your brain. This is presumed to prevent dementia.13 An overstressed and sleep-deprived brain produces proteins that are not correctly shaped. As these misshaped proteins build up, they can cause death of the brain cells: a hallmark of dementia.
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There is also new evidence that ketones provide chemical signals that protect neurons from injury, or the neurons repair themselves better in the face of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.
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Over 3 months, the mice with unlimited access to food developed the telltale signs of Huntington’s disease: severe disruption of normal sleep-wake cycle, poor motor coordination, and increased heart-rate variability. The mice in the TRE group were significantly protected from these symptoms. The TRE mice slept well, their movement was better coordinated, their heart rate was more regular, and their brain function was more similar to that of a healthy brain.
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Exercise increases brain-derived neurotrophic factor (BDNF), which strengthens the connection between neurons and improves memory. BDNF can further augment repair of stressed or injured neurons—the process that also occurs when a strong circadian clock is present in the brain. Both exercise and TRE can act independently or together to protect against the loss of dopaminergic neurons that happens in Parkinson’s disease.
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Having a strong circadian clock is a protection against the stresses of everyday life that affect our health. For instance, the stress hormone cortisol is under strong circadian regulation. In healthy people, cortisol production peaks in the morning and reduces to a minimum level around bedtime. This allows us to wind down and go to sleep.
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In a second mechanism, the circadian clock itself can negate the effect of a sudden spike in stress hormone production so that after the stressor is gone, we can return to a normal state of mind.
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You can maintain a robust clock and preserve your normal brain function by following four simple habits: sleep, TRE, exercise, and the appropriate exposure to daylight.
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few years ago, a direct connection was made between bipolar disorder and the circadian clock. One of the drugs used widely to treat bipolar disorders—lithium—was found to bind to one of the components of the circadian clock and make its function more potent.25 This finding has implications that are both preventative and therapeutic in terms of brain health. In the same way, we know that people without depression sleep better and have better eating habits than those fighting depression. But you don’t need lithium to achieve a positive mood; the circadian code habits of addressing sleep, light, food, and activity will help lift your spirits and improve brain health.
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L. Yin et al., “Nuclear Receptor Rev-erbα Is a Critical Lithium-Sensitive Component of the Circadian Clock,” Science 311, no. 5763 (2006): 1002–5.
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