Gallstones are hardened “stones” that form in your gallbladder out of Cholesterol or bilirubin. Cholesterol and bilirubin are 2 components of bile: a substance stored in the gallbladder and released when we eat.

If the gallbladder doesn’t empty properly or bile has too much cholesterol in it, this causes gallstones. They’re quite painful and affect 3 million people every year.

One important thing to know about bile is that it’s under heavy circadian regulation. All aspects of it including:

• Production in the liver
• Storage in the gallbladder
• Secretion by the gallbladder
• Recycling from the gut back to the liver

Around 95% of the bile we make is recycled every day; we only lose 5% in our feces. But when our circadian rhythms become disrupted, this disrupts bile flow and leads to gallstones.

I’ve mentioned the importance of optimizing circadian rhythms to prevent chronic disease numerous times on this blog.  The evidence is clear that circadian disruption dramatically increases the risk of multiple chronic diseases.

There’s also clear evidence that circadian disruption increases the risk of chronic disorders of the gut too. It also 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 circadian disruption and several chronic diseases in a study published in Finland.  It’s quite surprising to see which one is by far the strongest: 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.

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Circadian rhythms and bile release

The first blog I wrote on circadian rhythms and the gut covered this topic. (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.  Both the central clock and multiple peripheral clocks regulate proper bile output. So it’s evident that circadian disruption has a 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 is typically low in Western diets.  There’s also an upper limit to how much fat we should consume. Since 95% of bile acids are recycled, and this takes time, we can’t eat unlimited fat.

Unfortunately, we really have no clear objective way to determine if someone is experiencing circadian disruption.  Instead, we have to use surrogate markers as proxies such as:

• Total sleep
• Sleep quality
• Seasonal affective disorder questionnaires
• Mood questionnaires
• Morningness-eveningness questionnaires

Total sleep, sleep quality, and chronotype(morningness-eveningness) are pretty straightforward measures of circadian disruption.  Low levels of crappy sleep are signs that one is experiencing circadian disruption. Circadian rhythms tightly control our sleep.  Chronotype is essentially a gene/environment interaction 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.  But it’s caused by seasonal changes in light exposure. It;s also corrected by increasing light exposure. Thus, it makes sense as a useful measure of circadian disruption.  It also shows why Finland is a great place to use SAD as a marker of circadian disruption. Light exposure changes dramatically throughout the year there.

Circadian disruption is strongly associated with gallstones

This study uses something called an odds ratio. An odds ratio shows how one factor changes the odds of a person getting another. Assume the odds of someone with blue eyes being male is 1 in 2 but those with brown eyes is 1 in 4. The odds ratio of someone with blue eyes being male is twice that of someone with brown eyes. So the odds ratio is 2.

The odds ratio between measures of circadian disruption and gallstones was by far the strongest found in this 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. This is pretty crazy since SAD is 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 have gallstones than those with good sleep.  In the second, people with poor sleep were 21x more likely to suffer from gallstones than people with good sleep.

Finally, people who were night owls were 5.24x more likely to suffer from gallstones than 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.

Conclusion

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

Fortunately, a study recently published in Finland indicates that circadian disruption a strong piece of the gallstone puzzle.  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 lower 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 like they’re a walk in the park.  So, if you have a history of gallstones, it’s probably best to pay some mind to your circadian rhythms.

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