The biohacker’s guide to preventing leaky gut

Given the focus of this blog, you can imagine that I feel preventing leaky gut is pretty important to overall health.  This doesn’t just apply to people who are dealing with functional gastrointestinal disorders such as IBS, SIBO, and IBD. It also applies also to health and longevity as a whole. 

There’s a ton of evidence linking “leaky gut” to many of the chronic diseases of aging. Including things such as obesity, type 2 diabetes, cardiovascular disease, and Cancer. So, basically, most of the things that will end up killing you.

A recent paper looked at leaky gut and longevity.  The paper found disease-free centenarians living in a Blue Zone had lower levels of markers of leaky gut than healthy 40 year olds.  When compared to 40 year olds who had just had a heart attack, the gut of centenarians was even better.

Preventing leaky gut is one of the best ways to avoid chronic disease. And with it, the multiple years of declining health that comes with it.  This is primarily through a reduction in age-related chronic inflammation, also called “inflammaging”. 

Unfortunately, most people think they’re going to throw some probiotics and fiber at their gut and they’re good.  This would be like believing you could grow tomatoes in weed-ridden concrete by simply throwing some seeds in it.

On the contrary, I believe probiotics and fiber are healthy and potentially useful. But lifestyle is going to be the primary driver of the pristine, weed-free, nutrient-rich soil that is your gut.  So to even get those things to be useful, you need to fix lifestyle first.

But, how do you this?  Welp, you’re in luck.  Here are the top 9 ways you can prevent leaky gut by changing your lifestyle.

1)Optimize your circadian rhythms

Circadian rhythms for preventing leaky gut
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Basically, every aspect of your physiology is in some way regulated by your circadian rhythms.  Circadian rhythms help optimize function by translating environmental signals in to biological outputs.  For example, you wake up every day because your body can anticipate when it’s time to wake up. This is based off your habitual exposure to light, feeding, and physical activity.  If this didn’t happen, going to sleep in a dark room would be terminal.

Most functions of your gut are circadian in nature, including leaky gut.  Circadian disruption in mice, whether you induce it by deleting genes or changing environmental exposures, causes leaky gut.  This makes your gut leakier at all times. And worse, it makes it leakier than normal when you’re exposed to things that induce leaky gut. 

Just a note in humans, all of the chronic diseases I mentioned in the introduction typically correlate with circadian disruption. This makes optimizing circadian rhythms a crucial aspect of preventing leaky gut.

For more on circadian rhythms and how to set up your life to take advantage of them, click the link at the bottom of this blog post.

2)Don’t make a habit of taking NSAIDS

There’s a long history of data supporting the fact that non-steroidal anti-inflammatory drugs, including ibuprofen, cause leaky gut.  A review of the topic found”

“Virtually all studies agree that all conventional NSAIDs increase intestinal permeability in the human within 24 h of ingestion and that this is equally evident when they are taken long term.” 

A recent study found that this artifact of NSAID use may predispose to Non-alcoholic fatty liver disease.

Of course, this doesn’t mean that you can never take them and that you shouldn’t take them when prescribed.  What it means is that you probably shouldn’t use over-the-counter medicines such as ibuprofen(Advil), aspirin, or naproxen(Aleve) on a chronic, daily basis to manage pain.  Common examples include managing headaches, menstrual pain, or hangovers.

3)Limit alcohol

Limit alcohol for preventing leaky gut
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Any amount of alcohol can cause leaky gut.  Really, that about sums it up.  If you’re going to consume alcohol, do it wisely.  Basic recommendations are:

  • Consume it in moderation
  • Don’t consume it at night
  • Not on back-to-back days
  • Don’t consume it without optimizing circadian rhythms first

A special note. Alcohol-induced leaky gut was one of the behaviors exacerbated by circadian disruption in the study referenced in #1 above.

This relationship has actually been observed in humans. People working the night shift, a classic example of circadian disruption, have greater levels of intestinal permeability than day workers when exposed to alcohol.

4)Maintain a healthy weight/body mass index(BMI)

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Two recent studies found a moderately strong correlation between body mass index(BMI) and measures of leaky gut in adolescents.  Each study found this correlation despite using different measures of leaky gut.

The first found higher levels of lipopolysaccharide(LPS) in the blood.  LPS levels also correlated with elevated liver enzymes.  The second study found higher levels of lipopolysaccharide-binding protein(LBP). LBP does exactly as its name suggests when LPS enters the blood.  At any rate, maintaining a healthy weight is likely very important in preventing leaky gut.

Note: If you carry a lot of muscle mass, BMI may not be a great measure for you. Body fat percentage or height to waist ratio may be better.  However, for 95% of the population BMI works just fine.

5)Calorie restrict, or put another way, don’t over-consume calories

Getting people to calorie restrict is extraordinarily difficult; they certainly aren’t going to do it based on any mouse study.  Fortunately, we have a human study in obese women showing a very low calorie diet decreases leaky gut by 3 different measures.  And before anyone jumps in and says this is probably via weight loss…The change was reversed almost immediately after increasing calories and prior to weight regain.

In other words, high calorie intake independently of weight gain increases leaky gut, at least in obese women.

6)Get adequate sleep

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Sleep is important for health for so many reasons, not the least of which is to prevent leaky gut.  A study in mice found that sleep fragmentation caused leaky gut, but a return to normal sleep reversed it.  This effect is believed to be due to changes in the microbiome as:

  1. Sleep fragmentation changed the microbiome in mice
  2. Leaky gut could be transferred to other mice via fecal microbiome transplant
  3. The microbiome and gut leakiness returned to normal upon resolution to normal sleep.

Important point: It’s perfectly normal to wake up a few times every night, particularly after each sleep cycle.  That’s not the same as the sleep fragmentation used in this study.

7)Avoid hyperglycemia

Hyperglycemia is quickly becoming a more respected cause of leaky gut. Thanks in large part to a study published early last year.  The researchers found that inducing hyperglycemia in mice caused leaky gut. Leaky gut occurs because the way cells process glucose gets altered.  Taking it a step further, hemoglobin A1c matched up with bacterial products in the blood. Hemoglobing A1c is a measure used to estimate your average glucose over the last 3 months,

So, in a nutshell, there’s a strong argument that hyperglycemia causes leaky gut.  For a closer look at the study, check out my review of the study here.

8)Consume fewer meals

Just like getting people to reduce their calorie intake is difficult, getting them to cut back on their number of meals is difficult as well.  Fortunately, again, we have a human study to the rescue.  The study looked at meal size and frequency in obese and lean women.

What they found was that women had lower LPS levels when they consumed 2 meals than when they consumed 5.  This study was strongly controlled in that the women ate exactly the same food and calories in both conditions. The only difference was the number and size of each meal.  Lean women had lower levels of LPS in their blood during both conditions than obese women. But, lean women had higher LPS levels when they consumed 5 meals than when they consumed 2.

This is a pretty clear indication that consuming fewer meals reduces your risk of leaky gut.

9)Avoid toxic relationships

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This may seem shocking to people, but stress in general can increase leaky gut.  To illustrate this, researchers recently observed couples fighting, measured their levels of hostility, and measured the leakiness of their gut.  In short, couples with more hostile encounters had greater LBP than couples with less hostile ones.

Additionally, couples with hostile encounters had elevations in inflammatory markers that came with leaky gut.  So, marry wisely.


Whether you’re a biohacker looking to live a healthy life forever or someone trying to fix a damaged gut, lifestyle is the first line of defense for preventing a leaky gut.  Following the 9 strategies listed above can help you prevent or reverse leaky gut.  In fact, I would put a lot more weight to these behaviors than any supplements you’ll ever find.

You may notice that avoiding certain foods such as gluten or dairy are absent from the list.  Those foods can be problematic for some people. However, I believe sensitivity to those foods may be more of a symptom than a cause in most of people. A big part of this may be mediated by the microbiome. The microbiome improves by correcting lifestyle and short term restriction of inflammatory foods.  That said, if you have Celiac disease, don’t eat gluten.

Need help optimizing your circadian rhythms?  Many people jumped in on blocking blue light at night and time-restricted feeding. But there’s so much more to circadian rhythms than just these 2 habits. 

How much more?  I’ve put together a program that’s 16 hours of powerpoint presentation videos covering everything you need to know about optimizing your circadian rhythms.  If this piques your interest, check out my Circadian Retraining Program here.

9 thoughts on “The biohacker’s guide to preventing leaky gut

  1. peteranddebbie says:

    Have you come across any evidence that eliminating parasites – in particular Blastocystis – is important? Thanks.

    • cincodm says:

      I’m sure it is, but the question is is the parasite causing the problems or is the presence of the parasite indicative of a problem? I think it’s more likely the latter, or at the very least it is some other parasite coupled with the Blasto exposure that is problematic.

  2. Arie says:

    David, no clue why your site isn’t getting 10X the visitors and exposure. I’ve been doing a lot of research on gut health for the last year, and you’re one of the few that goes deep into everything.

    A question regarding alcohol: I’m 26 and occasionally drink with friends till late at night. That’s a triple blow of alcohol + circadian rhythm disruption + sleep deprivation. Would you recommend fasting till dinner the next day for damage control?

    I understand the best way to prevent harm is not drinking and going to bed at 10PM, but that’s a boring life.

    I assume the longer fasting will:
    – prevent food from entering the gut that is still recovering from the blows it got
    – allow ghrelin to prepare and heal the gut
    – let the body divert more resources to recovery instead of digestion

    Are these assumptions correct? Or do you recommend other strategies to prevent harm?

    Found your site yesterday, but binge-reading every article from the start.


    • cincodm says:

      Hey Arie, yeah, giving your gut a break is probably a good idea. Even when I stop drinking at a normal time I generally do that. Replacing B vitamins and increasing choline intake are also valuable.

      Thanks for the compliments! My goal is to make this the best site for gut relevant info. It’s definitely taken quite a bit of time and work to get to my 20 site visitors. I think the big issue is people don’t understand how much their gut health is driven by their behavior. So in addition to putting out the info, I have to figure out how to get people to realize the value. Thanks for reading!

  3. Lee says:

    Because of the hormone differences in men, what will make a man obese may not effect a woman. What will make women obese may not effect a man. Often times they try a one size fits all for people and even a woman’s hormone levels have to be considered. The commonality I found with many women is they were either under a lot of stress or had unresolved trauma they were holding onto.

    • cincodm says:

      I agree. I mean, at the Enid of the day, positive energy balance causes obesity. But the drivers of that surplus are certainly different between men and women.

      In fact, it’s different for everyone. Couldn’t agree more that unresolved trauma is a big driver for many.

      Thanks for reading!

      • Lee says:

        Very true trauma is one thing that can make men or women obese. It can almost completely shut down mitochondria function. You are amazing. How did you learn these things? This information is not something that can be found. These are things a person has to learn by connecting all the pieces of the puzzle. You are the only one I have seen that is getting the whole picture.

      • cincodm says:

        Thanks, Lee! I’ve been in fitness for 25 years so I’ve read a lot and learned some things through trial and error.

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