Taken from: http://eyesonnews.com/wp-content/uploads/2015/06/human-circadian-biological-clock1.png

Within you are trillions of tiny little timekeepers that keep things running on a schedule.  These timekeepers ensure that your body runs like a perfectly timed orchestra performing a musical masterpiece.

Typically the performance goes smoothly, with nary a missed note or beat.  However, messing with the timekeepers can ruin the performance.  Messing with the conductor can make it downright terrible.

Every cell in your body contains genes that help you run on a 24 hour cycle.  These genes are collectively called the circadian clock.  The master clock, found in the brain, is the conductor of the orchestra.

Located in an area of the brain called the suprachiasmatic nucleus, the master clock naturally runs a little over 24 hours with or without feedback.  When given feedback, it will run perfectly in tune with the light and dark cycles of the day.  The master clock is set by exposing the eye to light during the day, specifically blue light, and then not, during the night.

The peripheral clocks, those found in cells outside the central nervous system, work in concert with the master clock to help your body run like that well-tuned and timed orchestra.  The clocks effectively group cells with common and complimentary functions together so that when one cell sends a signal, the other is ready to receive it and respond appropriately.

These clocks are more in tune with energy metabolism than light.  They also integrate multiple systems together to ensure that energy metabolism, hormone secretion, immune function and basically every biological process in your body works properly.

It’s very important to have your clocks in tune with one another.  A number of important processes in the human body follow a circadian variation, hitting peaks and valleys at specific times of day.

For example, the hormone insulin is secreted by your pancreas to increase glucose uptake by muscle cells.  Your cells follow a circadian rhythm with regard to insulin sensitivity.  This means that at certain points of the day your cells will respond better to insulin than at other times.

Cortisol, an important hormone that helps you adapt to stress, follows a circadian pattern as well.

Taken from: http://nickelridge.ca/wp-content/uploads/2013/02/Cortisol-Circadian-Rhythm.png

Cortisol is a stress hormone that promotes alertness and a great example of a hormone that’s regulated by the circadian clocks.  This graph shows the circadian rhythm, also known as diurnal variation, of cortisol release.

Notice how cortisol peaks right around 6am and sharply drops off in the evening.  These two times coincide with awakening and winding down before bed.  If the circadian clocks involved with cortisol release are thrown out of sync and shifted by a couple of hours, you may have problems falling asleep at a decent hour and/or difficulty waking up in the morning.

Melatonin is another great example of a hormone that follows a circadian rhythm.  It also just so happens to be something that helps set the master clock and syncs it with the environment.

Throughout the day, melatonin secretion is blocked when the eye is exposed to blue light from the Sun.  After the Sun goes down and your eye is no longer exposed to blue light, the pineal gland begins secreting melatonin to signal your brain to wind down and begin the process of going to sleep.  If this process is interfered with, you can disrupt your circadian clocks.

When your circadian clocks become disrupted or out of sync, dysfunction ensues.  Typical symptoms of disrupted clocks include:

• Brain fog/Memory problems
• Pain/Migraines
• Fatigue
• Adrenal dysfunction
• Sex hormone imbalance/infertility
• Blood glucose dysregulation
• Weight gain
• Poor thyroid function
• Impaired immunity
• Digestive problems
• And more…

A lot of emphasis has been put on keeping your peripheral clocks synced up to your master clock, but there’s actually another clock you need to pay attention to.  This clock, your microbial clock, coordinates with the master clock and the rest of your body via the liver.  It’s very important to keep all your clocks in tune for optimal health.  Let’s take a look at how you do that.

Taken from: https://i1.wp.com/neurosciencenews.com/files/2016/12/microbiota-circadian-clock-neurosciencenews.jpg

The microbial clock

Over the last 2 decades, a ton of research has been done on the gut microbiome.  The gut microbiome is a collection of microogranisms that reside in the gut and have a huge impact on your physiology.  These bacteria snack on food components that you don’t digest or absorb and release metabolites in the gut that alter function throughout the body.

When these metabolites are released in to the blood, the first place they go is the liver.  Here, they help coordinate the liver clock.  Since the liver regulates many processes such as energy metabolism, hormone balance, detoxification, and digestion, this can have a major impact on your health.

But that’s not all.  The way the liver regulates many of these functions involves processing hormones and toxins in to bile and dumping them in to the gut.  In this way, the liver clock also helps regulate the microbial clock.  And if you think about it, by helping regulate energy metabolism throughout the body, the liver clock also regulates all the peripheral clocks.

What we know to this point is that the microbiome communicates with the liver clock and alters our internal physiology through metabolites generated in the gut(1, 2).  This can cause pretty profound changes in many biological processes, a great example of which is detoxification.

Detoxification and out of sync clocks

You may not be aware of this, but pharmaceutical drugs tend to be more effective during certain parts of the day.  This is because they’re processed in the same way that toxins are processed and this follows a circadian rhythm(3, 4).

Microbial metabolites can induce these pathways as they’re also processed in the same way.  Current research shows that microorganisms that make up our microbiome have their own circadian rhythms that are dictated by nutrient availability(5, 6).  This indicates that timing is of critical importance…to setting your clocks…go figure.

Detoxification is a fantastic example of what can go wrong when your master, peripheral, and microbial clocks get thrown out of sync.  Detoxification involves a large number of tissues throughout the body that must be in sync in order to work properly.

The whole process of detoxification involves the biotransformation of toxins in most tissues, but particularly the liver and gut, and excreting them through the kidneys or gut.  Sometimes the first phase of detoxification actually makes molecules more toxic, and if the second and third phases don’t occur concurrently, there can be a build up of ttoxins.  Again, Timing is everything.  For more on detoxification, I broke it down in a blog you can read here.

With age your clocks become out of sync and the entire process of detoxification becomes less efficient(3).  But you don’t need to get old to throw your clocks out of sync with one another.  You can just send the wrong signals to your clocks and they’ll gradually become out of sync.

Taken from: http://jeffreysterlingmd.files.wordpress.com/2014/02/swsd.jpg

Consequences of poorly synced clocks

There’s a large pool of evidence showing what happens when the circadian clocks aren’t properly synced.  Numerous studies show how disrupting sleep patterns alters metabolism, hormonal balance, immunity, and the microbiome.

In mice, disrupting circadian clocks…

• Increases leakiness of the gut and increases toxicity of alcohol to the liver(7)
• Alters the microbiome(8)
• Disturbs bile and lipid homeostasis(9)
• Increases susceptibility to gut infections(10)
• Alters glucose metabolism by inducing insulin resistance(11)

It’s hard to study these things in humans because controlled trials would be unethical.  What we do know is that people who work the night shift have substantially larger risks for obesity, cardiovascular disease, and Type 2 diabetes.  This is likely due, in large part, to disruption of circadian clocks from altered sleep habits and light exposure out of sync with the day/night cycle(12).

Taken from: http://www.nature.com/nrrheum/journal/vaop/ncurrent/images/nrrheum.2015.31-f1.jpg

Syncing your master clock to the environment

Having flexibility in setting your clock to the environment is important for survival.  We are diurnal creatures, active during the day and asleep at night.  If food was no longer available during the day, being able to shift when we sleep would be necessary for survival.  Having no flexibility would be a terrible survival strategy.

Cues from the environment help set our circadian clocks.  We already know that the master clock works best when synced up to the day/night cycle.  This means we can manipulate our exposure to light to help sync the master clock to the day/night cycle.

There are 2 important times of the day to regulate your light exposure.  First, upon awakening, you want to expose your eyes to light whether it be from the Sun or the lights in your house.

Specifically, blue light helps set your master clock by shutting off melatonin production by the pineal gland.  You shouldn’t have a problem finding blue light…your lights, TV, computer, and basically every light in your house that isn’t an amber or red light has some blue light.

Unfortunately, our ease in finding blue light makes it very difficult to avoid at night.  This is when you want to limit or eliminate your exposure to blue light.

When blue light no longer hits the eye, the pineal gland begins secreting melatonin which signals the body that it’s time to get ready for bed.  Exposing yourself to electronic devices and lights in your house blocks this signal.  Fortunately, there are ways to get around this.

There are screen filters such as F.lux or Unblue that you can use on your computer or handheld device that removes blue light from them.  There are also uber-expensive light bulbs you can buy that don’t emit blue light.

However, your television casts a fair amount of blue light so a more universal and extremely cheap solution is to buy blue blocking glasses.  These glasses work by blocking blue light at your eye, preventing the need for expensive bulbs or avoiding the TV or other electronic devices at night.

Taken from: http://d13geadg2uyg93.cloudfront.net/content/jap/107/6/1972/F1.large.jpg

Syncing your liver and peripheral clocks

Another important aspect in setting your circadian clocks is food consumption.  Generally, when people focus on food, they tend to focus on quality of diet.  However, when you eat is equally important as it will help set your liver clock.

The peripheral clocks in your body, including the liver and microbial clocks, are set by food timing.  More specifically, feeding/fasting times.  This is an important consideration for most people living in the US today because very few people employ significant amounts of fasting time.

It’s not uncommon for many people to eat 3 meals a day with 2 snacks wedged in between those meals.  This makes meals spaced out throughout the entire day AND gives very little break between each meal.

This isn’t a great situation, particularly considering the migrating motor complex, which sweeps the gut clean during these breaks between meals, has a pretty large effect on the microbial clock.  Eating stops the migrating motor complex in its tracks.

Probably the simplest way to look at this is that our master clock is optimized when it’s set based off cues from our external environment.  For us, light and food availability are the 2 factors that have the greatest effect on our circadian clocks and, thus, the circadian rhythm of various hormone and neurotransmitter secretions.

But these internal factors of ours, are external environmental factors for the microbial clock.  The microbes in our gut don’t see light, they sense nutrient availability and diurnal variations in hormones(Cortisol, melatonin, thyroid hormone, sex hormones), toxins, and bile secretions pumped in to the gut by the liver.  Bile flow in and of itself is pretty important because it keeps the microbial clock synced by restricting the growth of pathogens, promoting the growth of commensals, and preventing overgrowth of both.

So, to get our liver and microbial clocks synced to one another we need to tweak meal timing moreso than meal quality, although meal quality is also important. Meal quality will help set the types of bacteria that make up the microbiome while meal timing will set the rhythm of microbial metabolites as well as when microbes interact with the gut wall and liver clock(13).

The circadian interaction between the microbial and liver clocks will affect a number of aspects of your physiology.  Blood glucose management, detoxification, hormone balance, digestion, and the immune system just to name a few.

There’s a bit of research in to this and the consensus seems to be that fewer total meals, starting earlier in the active period, tends to be best.  Also, ending meals earlier in the afternoon and having a longer fasting window helps optimize circadian timing(14).  Studies in humans confirm these findings(15, 16) and show alterations in energy metabolism as well as cortisol rhythm.

Other potential factors for syncing your clocks

There are likely other factors that help sync up your circadian clocks.  The peripheral clocks are regulated by food via energy metabolism.  Physical activity and exercise are also ways to alter energy metabolism in the liver clock as well as muscle clocks(17, 18).

For much of our evolution, physical activity and eating have been paired together.  While this is currently not the case, most of our existence has required physical activity to procure and process food for consumption.

Another admittedly odd factor may involve our contact with the Earth.  Grounding refers to having contact with the Earth, normally with bare feet.  The hypothesis is that direct contact with your feet to the Earth allows you to absorb electrons through your feet.  These electrons enter your body and function in the way antioxidants do, by neutralizing free radicals.

It seems kind of cooky, but a very small study found that grounding while sleeping improved the circadian cortisol profile in people whose cortisol profile was disrupted(19).

Taken from: http://4.bp.blogspot.com/-2q9Dsu0mv4k/UeV1XA7kBbI/AAAAAAAAAdA/uEnMXggWNew/s

This study used a mattress pad ground to the Earth rather than bare feet.  It’s a very interesting study, but since there were only 12 participants I’m definitely not ready to say this is something with hard science behind it.  Fortunately it costs literally nothing in time, effort, or money to give it a try.

One final factor that I think may have some relevance brings us back to light exposure, but to the skin rather than the eyes.  There are 2 routes by which exposure of the skin to the Sun may have an effect on syncing circadian clocks.

First, we know that exposure of skin to the Sun ultimately regulates vitamin D levels.  Vitamin D is involved in a ton of processes, and a newly discovered one is the expression of circadian clock related genes(20).

Another factor unrelated to vitamin D is that the skin contains receptors that are responsive to light(21).  This doesn’t necessarily mean that they have an effect on circadian clocks, but it certainly raises a question as to why the skin contains receptors sensitive to light.

While these mechanisms are certainly interesting, they require far more study before I’d put any weight behind them.

Taken from: http://4.bp.blogspot.com/_-7ybFsiE-ek/S-w963YKYdI/AAAAAAAAAS8/75GFXqryLYk/s1

Conclusion

If you look at your body like a biological orchestra, you realize that timing is a pretty critical factor.  You want the horn section to come in when it’s supposed to and not get stepped on by the string section.  You also want percussion to hold the beat so that all other sections can play in a coordinated fashion.

In the same way, you want your master and peripheral circadian clocks to run in sync.  This is best accomplished by syncing your clocks to the environment.  Syncing your master clock is as simple as regulating when your eye is exposed to light during the day/night cycle.

Your peripheral clocks have a different way of keeping in sync.  They sync up to feeding and fasting cycles.  Meal timing and meal frequency are key to syncing these clocks.

Your microbial clock is a new player in the circadian clock game.  The microbial clock is also regulated by feeding and fasting cycles and interacts with the liver clock to help regulate host metabolism.  This can change all systems, but especially hormonal balance, energy metabolism, immune function, and detoxification.

All of your circadian clocks are meant to adjust your physiology to your external environment.  This changes your internal physiology which, in turn, changes the environment that your microbial clock is exposed to.  Keeping everything in sync is ideal for optimal health.