by Siim Land
Don’t Be Afraid of Hunger – Most people have manic fear of going hungry. It’s more psychological than physical. Fasting can actually help you to reconceptualize hunger and associate it with more vigor and success.
Don’t Make It a Big Deal - If you think that you may potentially damage yourself, then you probably will, because of creating a stress response with your mind. Choose to see it as something that empowers not harms you and you’ll start to feel amazing.
Don’t Gorge After Fasting – It doesn’t matter how long you fast if you jeopardize it all by eating excessive amounts of calories and still gaining weight. Moderation is key, especially in fasting and eating.
In this chapter, we talked about different situations when you should not do intermittent fasting but all gets tied back to still doing it. There are no real reasons why you shouldn’t do intermittent fasting and there’s always a way to make it work. You just have to know what kind of a signal are you sending to your body and how to leverage it according to your goals.
The concluding message would be that you should fast and time restrict your eating despite the day or what your condition is. Just modify it. Don’t become dogmatic either and you can safely have random bouts of eating and fasting as you wish as long as you just do it.
Chapter XXI
Circadian Rhythms and Autophagy
“We can easily forgive a child who is afraid of the dark;
the real tragedy of life is when men are afraid of the light.”
Plato
Many life forms follow certain patterns of behavior that are linked with the day and night cycles of the planet. Virtually all animals have some sort of a sleeping routine. There’s also evidence for the presence of internal clocks that regulate the body’s biological processes based on daytime. However, these biological rhythms appear to be present even in the absence of external cues, such as light and temperature.
In 1729, a French scientist Jean-Jacques d'Ortous de Mairan saw how the 24-hour patterns in the movement of the leaves of Mimosa pudica remained constant even when the plant was kept in continuous darkness[654]. These endogenous cycles were first independently discovered in fruit flies in 1935 by two German zoologists, Hans Kalmus and Erwin Bünning[655].
The term circadian was coined by Franz Halberg in 1959 who said:
The term "circadian" was derived from circa (about) and dies (day); it may serve to imply that certain physiologic periods are close to 24 hours, if not exactly that length. Herein, "circadian" might be applied to all "24-hour" rhythms, whether or not their periods, individually or on the average, are different from 24 hours, longer or shorter, by a few minutes or hours.[656]
In 1977, the International Committee on Nomenclature of the International Society for Chronobiology adopted the official definition for circadian rhythms, which goes like this:
Circadian: relating to biologic variations or rhythms with a frequency of 1 cycle in 24 ± 4-h; circa (about, approximately) and dies (day or 24 h).
Note: term describes rhythms with an about 24-h cycle length, whether they are frequency-synchronized with (acceptable) or are desynchronized or free-running from the local environmental time scale, with periods of slightly yet consistently different from 24 hours[657].
In 2017, three scientists Jeffrey C. Hall, Michael Rosbash and Michael W. Young were awarded the Nobel Prize in Physiology or Medicine for their discoveries of molecular mechanisms controlling the circadian rhythm[658]. During their research, the men identified a gene in fruit flies that controls their circadian rhythms. They named this gene period, which encodes a protein called PER. PER accumulates during the night and degrades during the day, thus it oscillates over a 24-hour cycle, in synchrony with the circadian rhythm.
Figure 93 The 2017 Nobel Prize winners in Physiology or Medicine
Circadian rhythms enable living organisms to prepare for and adapt to environmental changes that happen on a regular basis. For instance, the coming winter, nighttime, seasonality of certain food sources, faunal mobility, and fluctuations in climate. By now we know that almost every organ and individual cell has its own biological clock that’s regulated by the master clock in the brain[659].
In regards to health and nutrition, circadian rhythms play an immense role. They’re going to dictate what kind of physiological processes to commence and which hormonal patterns to follow. That’s why it’s a vital component to the regulation of autophagy, growth hormone, fat loss, insulin sensitivity and much more.
Let’s go through some of the basics. What are circadian rhythms then?
Circadian Rhythm Basics
Circadian rhythms are biological rhythms inside your body that are connected with the day and night cycles of the environment. Humans are diurnal creatures, which means we’re active during the daytime and sleep at night. Rats and owls are nocturnal – they’re active at night and sleep during the day.
With these circadian patterns come distinctive physiological processes that have evolved over the course of eons. They’re evolutionary adaptations of creatures living in a certain way that promoted their survival and evolution.
That’s why there’s some genetic variance to every person’s circadian code. Think of night owls and morning larks who sleep at different times. As hunter-gatherers, some people were more suitable for guarding the camp when others were sleeping etc. However, that difference is very small and differs maybe like a few hours. Humans are still evolved to be diurnal and when the sun’s out we better be sleeping.
There is no one whose natural circadian rhythm would be to be awake after midnight and sleep until noon. Those things are the result of living in a modern world with different type of circadian disruptors and lifestyle factors. Shift work, playing video games until the morning, and partying under fluorescent light is unnatural and one of the worst things for your health.
Early research in humans speculated that most people’s circadian rhythm is closer to 25 hours when isolated from external cues[660]. However, these results were misleading because the participants weren’t shielded from artificial light. In 1999, a Harvard study found that the human circadian rhythm is about 24 hours and 11 minutes, which is closer to the solar day[661].
Figure 94 Circadian Rhythms in Humans
What Affects Circadian Rhythms
There are 3 main signaling factors that affect the circadian rhythms – light, movement, and food. Most of the circadian signaling is transmitted through your eyes. When light enters the retinas and gets transmitted into the brain it stimulates the suprachiasmatic nucleus (SCN) (See Figure 95). The SCN is the master circadian clock in your body that regulates all the other biological rhythms and clocks. There are many different types of clocks and it’s thought that most organs like the liver, heart, and pancreas actually have their own circadian clock. That’s why all these different factors like sunlight, physical exercise, and eating affect the entire circadian rhythm of your body.
Figure 95 The Master Clock in the Brain is the Suprachiasmatic Nucleus or SCN
Light is made of many electromagnetic particles or photons that travel through space in a wavelength form. They emit energy and are represented by different colors (Figure 96). Sunlight’s wavelength is called the solar spectrum and it contains ultraviolet, visible, and infrared wavelengths.
Figure 96 The Light Spectrum
The human eye can only detect visible light which is seen as either violet, indigo, blue, green, yellow, orange, or red light.
Blue light is part of the natural environment and can be seen almost everywhere. The reason why the sky is blue is actually that the blue light coming from the Sun collides with the air molecules and makes the blue light scatter everywhere.
Blue light exposure to the eyes plays a very important role in regulating your circadian rhythms and day and night cycles. It has antibacterial properties, boosts wakefulness, increases alertness, and can adjust the circadian clock. Too much blue light at the wrong time can damage your mitochondria, promote insu
lin resistance[662], cause insomnia, depression, and increase inflammation.
Blue light has a short wavelength of 380-500 nM, which makes it produce higher amounts of energy. Naturally, you wouldn’t get exposed to much blue light aside from the early to afternoon parts of the day. However, ever since the invention of the light bulb, our environment has many additional sources of blue light. Because of technology and new gadgets, we’re getting exposed to more blue light for longer periods of time which can offset the circadian rhythm and cause damage to our health.
Blue light exposure at night and circadian mismatches are linked to many types of cancer, diabetes, obesity, heart disease, and Alzheimer’s[663]. You wouldn’t think that it has such a huge role but after you learn about how light affects your body’s biological processes you’ll realize how serious this actually is.
Melatonin is the sleep hormone and a powerful antioxidant that helps to conduct many repair processes in the brain and body. If you inhibit melatonin secretion because of blue light at night, then you’re going to lower growth hormone, which makes it more difficult for you to burn fat and build muscle, and you’ll also prevent the brain from clearing out the toxins that get accumulated there during the day.
There are these proteins called beta-amyloids that are associated with Alzheimer’s and Parkinson's and if you don’t remove them during sleep with autophagy they begin to accumulate there. Keep in mind that these neurodegenerative diseases happen over the course of decades and you can begin to show the first signs of Alzheimer’s 10-20 years already before you actually get the disease.
Figure 97 The Difference Between a Normal and an Alzheimer's Brain
So, if you’ve noticed yourself having brain fog, forgetfulness, or the inability to focus, then you should start taking your circadian rhythms and sleep quality a lot more seriously. I dare say nearly 70% of modern diseases are actually rooted in circadian rhythm mismatches not just eating too much and moving too little.
If you’re working at night shift or tend to stay up late all the time, then you have to seriously reconsider what time do you go to bed and what time do you wake up because it’s literally killing you.
Protect Your Circadian Rhythms
However, not all blue light is bad. The timing of when you get exposed to it matters a whole lot more, which is why you’d have to entrain yourself to follow a proper circadian rhythm.
Expose yourself to the natural sunlight first thing in the morning. This will synchronize your biological clock to the surrounding environments and maintains consistency.
If you live in an area where you don’t get much sunlight or if it’s cloudy, then use blue light emitting devices such as the Human Charger or face lamps for 10-15 minutes.
On days with clear sunlight try to spend more time outside by going for a long walk. This will raise vitamin D levels and charges up the mitochondria as well. The majority of circadian signaling happens through the eyes so try to expose them to the daylight. Don’t look directly at the sun but gaze the entire blue sky. Don’t wear sunglasses or hats that cover your vision either because you’ll miss out on the blue light.
When indoors wear long sleeve clothes to protect your skin from too much blue light exposure. A lot of the circadian signaling also happens through the skin, which is why you don’t want to sit under fluorescent lights before bed.
Wear blue blocking glasses in the evening. I’m using different blue blockers. The most effective ones are the Truedark ones that literally cover your entire eyes and make you look like Vin Diesel from the movie Riddick but there are less scary ones like BluBlox that actually look stylish and something you could wear in public.
Install a software called F.lux or Iris on your computer to automatically match the brightness of the screen with the circadian rhythms. On Android, it’s called Twilight.
Sleep in pitch black darkness with blackout blinds and a sleeping mask that covers your eyes.
Make sure there are no hidden sources of blue or green light in your house like the alarm clock, night lamps, red dots on the TV screen, smoke detector lights and so on.
When you do some research, then you’ll find that blue light at night really is quite scary stuff and it’s going to shut off melatonin production.
Food Intake and Circadian Rhythms
Another critical component to circadian rhythms is food intake. It turns out that the timing of when you eat is even more important to your health than what and how much you eat.
Time-Restricted Feeding (TEF) emerged as a concept within the context of circadian rhythms. The master clock is very connected to nutrient sensing pathways that detect the presence of calories and food[664].
In most animals, feeding is confined to a certain time period, which leaves a short period of fasting that coincides with sleep. Unfortunately, modern life not only disrupts our circadian rhythms with light but also with food. An average person in the Western world tends to spend most of the day in a fed state, leaving no time for the body to heal itself. Some people can even eat right before going to bed, sleep for about 7-8 hours, and start eating immediately after waking up. This prevents them from ever entering into fasted conditions that are so vital for longevity.
Dr Satchin Panda, who is a professor at the Salk Institute and an expert in circadian rhythms, recommends people to eat their food within a minimum of 8-10 hours. During fasting, the gut and immune system have then enough time to repair themselves and conduct other autophagic processes. Dr Panda’s research has found that the average person eats over a 15-hour period, starting with a drop of milk in their morning coffee and ending with a late night snack of some nuts or chips[665].
In 2015, a study tested how eating an entire day’s caloric intake within 10-11 hours affect overweight individuals. Their eating window ended around 8 PM. They lost about 4% body weight in 16 weeks and retained it for up to a year. This was accompanied by a spontaneous 20% reduction in calories just because of skipping out on random snacks or alcohol late at night. The participants also reported improved sleep and higher alertness during daytime.
Time-restricted feeding has also been shown to prevent metabolic disorders in mice who are fed a high-fat diet without reducing calories[666]. The mice who were fed their food within 8 hours didn’t get obese or develop disease compared to those who ate the same amount of calories with no time restrictions.
Figure 98 The power of time-restricted feeding on weight loss
By this part of the book, you don’t need to be convinced about the benefits of intermittent fasting and time restricted feeding. A smaller eating frequency is in most cases more optimal for both body composition as well as the circadian rhythm. However, we still should learn about what’s the optimal time to eat food.
The Best Time to Eat
Cortisol, the stress hormone, is also highest in the morning. It starts rising at about 5-7 AM and peaks around 8 AM so that we could have the energy to get out of bed. At this point, cortisol is actually beneficial because it ignites the body’s fat oxidation mechanisms and initiates the circadian rhythm. However, as we’ve learned by now, it’s not a good idea to be eating anything with elevated cortisol. Instead, the best thing to do is to postpone it by at least a few hours.
Hunger also follows circadian rhythms. A study found that despite the extended overnight fast, paradoxically, people aren’t as ravenous in the morning and they tend to not want much breakfast. You’d think that the longer they’ve spent fasting the hungrier they’d get, but the opposite happened. No matter how long their fast had lasted, the participants still reported less desire to eat after waking up. Instead, the internal clock increased appetite in the evening, independent of food intake and other factors. Hunger ditches at 8 AM and peaks at 8 PM[667]. See Figure 99.
Figure 99 Circadian Rhythm of Hunger
This makes perfect sense, as after an overnight fast we’re in mild ketosis and utilizing fat for fuel. Ketone bodies tend to be appetite suppressing and prevent hunger, which is why a
healthy metabolism shouldn’t feel ravenous right after waking up.
Based on this knowledge, even if you’re not doing intermittent fasting, for optimal health, you’d want to postpone breakfast by at least a few hours. But what about other times?
During daytime, insulin production by the pancreas is much better than at night. Blood sugar control is also best during the earlier parts of the day and worse in the evening[668]. This makes perfect circadian sense, as blue light in the evening promotes insulin resistance and weight gain. Part of the reason has to do with how the circadian clocks in all of the organs and cells switch on and off synchronously at the same time of the day[669].
Melatonin levels begin to rise a few hours before habitual bedtime, given that you don’t get exposed to blue light. When melatonin rises, it can bind to its receptor in the pancreas, which essentially tells the pancreas to stop producing insulin[670]. Basically, the idea is that it’s not necessary to be releasing insulin anymore and it’s time to sleep. If someone’s having a big meal during that time, there might not be enough insulin to clear the bloodstream from glucose.
Figure 100 Melatonin at night inhibits the production of insulin.
High insulin at night probably inhibits melatonin as well.
However, all these studies miss the critical aspect of extended intermittent fasting that lasts for up to 20 hours a day. In those cases, the body will be extremely insulin sensitive regardless of what time of the day it is. Even when there is a minute 5-10% reduction in blood sugar control, the effects would be insignificant due to the already high state of insulin sensitivity.