New study highlights the importance of circadian rhythms to prevent gallstones

I’ve mentioned the importance of optimizing circadian rhythms to prevent and reverse chronic disease on a number of occasions on this blog.  In my opinion, the evidence is crystal clear that circadian disruption dramatically increases the risk of multiple chronic diseases, particularly the ones that kill us(CVD, T2D, Cancer, Alzheimer’s disease).

I think there’s also fairly clear evidence that circadian disruption plays a role in increasing the risk of chronic disorders of the gut, and makes the symptoms of those disorders much worse.  To see a summary of the data on that, click here.

So it didn’t really surprise me to see strong relationships between indicators of circadian disruption and an increased risk of several chronic diseases in a study recently published in Finland.  I was kind of surprised to see which chronic disease was far and away the one most associated with circadian disruption: gallstones.  And it’s not because I don’t think that relationship is strong; it’s because it was so much stronger than the other ones that it was pretty jaw-dropping.

Image result for circadian bile

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Circadian rhythms and bile release

One of the first blogs I wrote on circadian rhythms and the gut was entitled, “Is bile the key that turns the gut clock?”  In it I discuss how important bile is as an input and output of the circadian clock.  Since both the central clock and multiple peripheral clocks(liver, gut, gallbladder, adrenal) all play a role in proper bile output, it’s pretty evident that circadian disruption can have pretty powerful effect on impairing bile flow.

Light exposure, physical activity, and the feeding/fasting cycle are all zeitgebers we can use to optimize bile output.  Nutrient status is also important as healthy bile requires adequate phosphatidylcholine which can be attained via the diet, but is typically underconsumed in Western diets.  There’s also probably an upper limit to the amount of fat we should consume, because 95% of bile acids are recycled and this takes time.

Unfortunately, we really have no clear objective way to determine if someone is experiencing circadian disruption.  Instead, we have to use surrogate markers such as total sleep, sleep quality, seasonal affective disorder, mood, and morningness-evengingness questionnaires as proxies for circadain disruption.

Total sleep, sleep quality, and chronotype(morningness-eveningness) are pretty straightforward measures of circadian disruption.  Low levels of total sleep and sleep quality are generally signs that one is experiencing circadian disruption as circadian rhythms are one of the 2 primary drivers of sleep.  Chronotype is essentially a gene/environment phenotype that determines whether a person is an early-bird, night owl, or mixed type.

Seasonal affective disorder(SAD), on the other hand, may not seem that intuitive of a marker of circadian disruption.  However, when you take in to consideration that it is caused by seasonal changes in light exposure and corrected by increasing light exposure during times when it is low, you can see why it is a useful measure of circadian disruption.  It also indicates why a place like Finland, where daily light exposure changes robustly throughout the year, is a great place to use SAD as a marker of circadian disruption.

Circadian disruption is strongly associated with gallstones

When we look at epidemiological data, we can use several statistical methods to show how strongly 2 variables are related to one another.  In this study, they used something called the odds ratio(OR).  Simply put, an odds ratio tells you the odds of someone with x having y compared with someone without x having y.  For example, if your odds of having x is 1 in 2 and my odds of having the same are 1 in 4, the odds ratio of you having x compared to me is 2, or you are twice as likely to have x as I am.

Now, an odds ratio says nothing of causality.  It doesn’t say x causes y or y causes x, it simply indicates a relationship strong or small.  So on their own, epidemiological studies are simply useful for hypothesis generation or they must be combined with other mechanistic or clinical trial data to determine causality.

With this in mind, the odds ratio between measures of circadian disruption and gallstones is by far the strongest found in the study.  People with SAD are nearly 15x more likely to have gallstones than people without it.  The next strongest relationship with SAD was depression at 8.73, which is pretty crazy given that SAD is effectively seasonal depression.

There were 2 separate studies looking at sleep quality and gallstones.  In the first, people with poor sleep quality were 6.25x more likely to suffer with gallstones compared to people with good sleep quality.  In the second study, the news got much worse for people with poor sleep quality, as they were more than 21x more likely to suffer from gallstones than people with good sleep quality.

Finally, people who were night owls were 5.24x more likely to suffer from gallstones than people who were early birds or mixed.  All pretty striking relationships on their own, but when we look at the animal data, it’s pretty clear that circadian disruption is likely driving impaired bile output.  I covered that in blogs you can find here, here, and here.


Evidence in animal models indicates the many ways that circadian disruption can impair bile output.  Unfortunately, we don’t have any clinical trials in humans showing the effects of circadian disruption on bile output or gallbladder health because it’s not something we can measure directly.

Fortunately, a study recently published in Finland indicates that circadian disruption may be a critical piece of the puzzle in people with gallstones.  I say fortunately because this is a behavior that we can modify, and based on this study, it’s a pretty strong behavioral factor that can dramatically decrease your risk of developing gallstones.

Now, the absolute risk for developing gallstones is still quite low.  Be that as it may, they don’t seem as though they’re a walk in the park.  So, if you have or a family member has a history of gallstones, it’s probably in your best interest to pay some mind to your circadian rhythms.

Wanna learn more about how you can optimize your health using the science behind circadian rhythms?  I have an ever-growing program that can do just that called the Circadian Retraining Program, check it out here.

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