Does A Leaky Gut Cause Fatigue?

Did you know: a leaky gut could be behind your chronic fatigue.

Intestinal permeability or, leaky gut, has recently emerged as a potential culprit in chronic fatigue syndrome. In this post, we’ll explore exactly what a leaky gut is (not what the media wants you to believe) and exactly how a leaky gut contributes to fatigue. Let’s jump in!

What’s all this talk about leaky gut?

You’ve heard of the term leaky gut before, right?

Maybe you’ve heard it called intestinal permeability. Leaky gut, intestinal permeability, or, whatever else you may know the condition by, describes a state where your intestines are no longer functioning properly. Proper intestinal function keeps the bad stuff in your gut (and out of your blood) but lets the good stuff pass through your gut and into your blood.

Imagine your intestines to be like cheesecloth. Small particles can make their way through the cheesecloth and into your blood. Large particles cannot pass through the cheesecloth and remain in your intestines. You want the small particles entering your blood as these are all the vitamins/minerals/amino acids your body needs to function. You don’t want large particles making their way into your blood. If the large particles make it through your intestines, your gut is leaking!

In more technical terms, epithelial cells are what your cheesecloth is composed of. These epithelial cells are connected through something called tight junctions. Tight junctions are just that — very small (tight) spaces between your cells. In a healthy gut, these tight junctions are, well, tight! They don’t allow anything bad through. But when your gut starts to leak, these junctions are no longer able to keep the bad stuff out.

When your gut is leaking, it’s like you have large holes punched in your cheesecloth. Now, the large particles, that should remain in your intestines, can enter circulation. When these large particles enter your blood supply, they wreak all kinds of havoc. They increase levels of inflammation, they cause gut symptoms like pain and bloating, they cause food allergies/sensitivities, and they may even be behind your chronic fatigue!

What exactly leaks into your blood?

Ok, you now know that holes or, damage to your intestines allows large molecules from your gut to enter your blood (not good!). But there are specific bad things that you really don’t want to enter your blood supply. This includes things like:

  • Bacteria and their toxins (more on this below)
  • Undigested or partially digested food
  • Viruses
  • Parasites
  • Yeasts

Your body really doesn’t want any of the above items in its blood supply. It wants to keep all those bacteria, yeasts, viruses, parasites, etc. in your gut where they belong. Remember, your gut is your body’s first line of immune defense. If your gut is compromised, your immune system will be compromised.

Should any of the above make their way into your blood, your body is going to respond with an immune reaction. Immune reactions involve inflammation. Your body sends inflammation to the epithelial cells (your gut lining) and a broad/general inflammatory response throughout its circulation. An inflammatory response in your gut causes even more permeability. Which worsens the inflammation.

Pretty soon, you end up having a vicious cycle of inflammation. This is a perfect example of chronic inflammation in action. And if you have chronic fatigue syndrome, you’re going to want to do everything you can to lower inflammation. To best do this, look first to your gut!

Is your gut leaking?

I’m not one for assumptions, but if you’re dealing with chronic fatigue and have IBS-like symptoms, odds are high that you’ve got yourself a leaky gut. Some of the other symptoms associated with leaky gut include:

  • Rashes
  • Itchy skin
  • Rosacea
  • Hives
  • Headaches/migraines
  • Brain fog
  • Emotional disturbances — depression, anxiety
  • Food allergies/sensitivities
  • Diarrhea or constipation
  • Fatigue
  • Abdominal bloating

This is by no means a comprehensive list. I want to be completely clear that I do not advocate diagnosing yourself or someone else with leaky gut based solely on signs/symptoms. Proper lab testing is essential in objectively determining whether or not your gut is leaking.

How is leaky gut diagnosed?

Do not diagnose leaky gut based on your symptoms. This is called guessing. Instead, perform objective laboratory testing.

At our clinic, I like to use Cyrex Labs Array 2. This is a blood test that measures antibodies to the following markers:

  • Actomyosin Network
  • Occludin/Zonulin
  • Lipopolysaccharides (LPS)

Actomyosin network

The actomyosin network is absolutely essential for the tight junctions of your digestive tract to function properly. (1) It is this network that prevents the bad stuff (like bacteria/viruses/parasites, etc) from entering your circulation. (2) The actomyosin network signals your tight junctions to contract. This contracture or flexing of the tight junctions stops particles moving from your gut and into circulation. It’s as if they lift up the drawbridge. No one can enter now.

If your blood shows antibodies to the actomyosin network, this indicates either the infiltration of bacteria from your gut to your blood or an autoimmune disease targeted at your gut. Proper leaky gut testing should always also include occludin/zonulin and LPS antibodies.

Occludin and Zonulin

Remember how I said that the tight junctions of your gut are composed of specific cells called endothelial cells?

Well, zonulin and occludin are the building blocks of those tight junctions. (3, 4) If you have antibodies to either zonulin or occludin, it indicates that the normal regulation of your tight junctions is compromised. It also suggests that your tight junctions are breaking down due to an autoimmune mechanism. This could be triggered by environmental factors like infections, toxic chemicals, and even dietary proteins and peptides. (5, 6, 7)

To summarize, if you have antibodies to occludin or zonulin, you have a leaky gut. This will often precede a diagnosis of autoimmunity or chronic fatigue. (8) If you have a first degree relative with autoimmunity or CFS, I strongly encourage you to check the health of your gut! Fixing it now will help prevent the development of chronic fatigue or autoimmune illness.

Lipopolysaccharides (LPS)

LPS is a component of the surface membrane of bacteria found in your gastrointestinal tract. It is totally normal to find these inside your GI tract. It is not at all normal to find these in your blood. If you do find them in your blood, it is likely that you have a leaky gut.

LPS increases the charge of the bacterial membrane and promotes the upregulation of pro-inflammatory responses by your immune system. (9, 10) If you have LPS antibodies in your blood, you’re going to experience a very strong activation of your immune system. (11) Think, chronic levels of inflammation. This is something you’re going to want to remedy should you be fighting chronic fatigue syndrome.

How a leaky gut is connected to chronic fatigue

Some studies suggest that leaky gut causes chronic fatigue. (12) I’m not convinced leaky gut is the cause of CFS. I’m also not sure if leaky gut increases the risk of developing chronic fatigue or if chronic fatigue increases the risk of developing a leaky gut. Confusion aside, it really doesn’t matter. You can safely conclude that there is a connection between leaky gut and chronic fatigue. It may not be a causal relationship. But improving your gut function will improve your energy levels.

You know that a leaky gut increases inflammation in your body. And you know that inflammation is linked to adrenal fatigue and chronic fatigue. Heck, those with chronic fatigue syndrome are often found to have multiple markers for gut inflammation outside of healthy reference ranges. (13) This is likely why there are so many cases of IBS connected to chronic fatigue syndrome.

Those with chronic fatigue syndrome have been shown to have elevated levels of lipopolysaccharides (LPS). (14, 15, 16) Remember, if you have elevated levels of LPS in your blood, not only is your gut leaking but you also are likely to have a chronic inflammatory response. Elevated LPS levels on their own is not a conclusive diagnosis for leaky gut. You’d also want to see antibodies to the actomyosin network as well as zonulin/occludin. But the probability of there being a leaky gut is very high.

One small study even showed that once LPS levels decreased (likely indicative of repair to a leaky gut) participants experienced an improvement in fatigue, joint pain, and cognitive function. (17) Clearly, there’s a strong connection between CFS and leaky gut. The simple act of addressing your gut is likely to improve your energy!

How to heal a leaky gut

I want to be crystal clear that you cannot supplement yourself out of a leaky gut. You cannot continue to eat processed/refined foods, take a glutamine supplement and think that everything is going to be alright.

Recent research has shown that any gluten consumption temporarily affects tight junction function in your gut. (18) This occurs whether or not you are celiac, non-celiac gluten sensitive, or non-reactive to gluten. It occurs in everyone.

Therefore, in order to properly heal a leaky gut, you need to (at least) follow a strict gluten-free diet. If you’re dealing with chronic fatigue, I recommend starting with a fatigue reset diet. If you’re already comfortable eating whole foods, it’s time to move to the ideal diet for chronic fatigue — ketosis. Not only is the ketogenic diet incredibly anti-inflammatory, but research is also suggesting that it may even help improve a leaky gut. (19, 20)

Changing your diet is step number one. And it’s the most important step. If you don’t change your diet, you’re not going to heal your leaky gut. Once your diet has been altered, it’s time to start a supplement regime that has been shown to improve leaky gut.

Supplements for a leaky gut and chronic fatigue

I did a deep dive into the most beneficial supplements for chronic fatigue and leaky gut in previous posts. Here, I’ll give you the abbreviated version of what supplements you should be taking for a leaky gut and chronic fatigue.

Vitamin A & D

These fat-soluble vitamins have been shown to decrease the inflammatory response in your gut and improve the function of your tight junctions (thus, repairing a leaky gut). (21) They are absolutely essential in the proper treatment of a leaky gut. Not to mention a lot of you living at very high or low latitudes will need to supplement vitamin D in the winter months.

I recommend you source your vitamin A & D through a high-quality cod liver oil (CLO). CLO has vitamins A & D in a ratio that makes it available and ready to be used by your body.


Probiotics are beneficial strains of bacteria. But they’re not all created equal. To heal a leaky gut (and improve fatigue!), you’re going to want to take a high dose (>10billion CFU) of a multi-strain probiotic supplement. Multi-strain probiotics have multiple different species of bacteria in them. Look for predominantly bifidobacterium, Bacillus species, an/or Saccharomyces Boulardii (this is a beneficial yeast species).


Zinc has been shown to increase the functioning of your gut’s tight junctions. (22) Zinc deficiency can come about from celiac disease, IBS or IBD, food allergies/sensitivities, diarrhea, PPI medications, and/or malabsorption. (23) The recommended daily allowance for zinc is 11mg per day. Unfortunately, this is not nearly enough zinc to improve gut function. You’re going to want your zinc supplementation to be closer to 50mg/day. (24) Though this comes with a strong caution: do not take high doses of zinc for longer than 2 weeks. Doing so will alter your zinc-copper balance.


Is there was a celebrity supplement for leaky gut, it’s glutamine. Unfortunately, a small dose of glutamine is not going to improve your gut function. To exact a benefit on your gut function and fatigue levels, take a glutamine dose of 0.25–0.3g/kg of body weight. (25) If you’re a 150lb female (~68kg) you’ll want your glutamine dose to be 17g — 20g each day.

In addition to the above supplements, ensure your diet consists of both raw fermented foods and prebiotic fiber. Prebiotic fiber is also known as soluble fiber. Think of it as food for the good bacteria in your gut. To improve fatigue and leaky gut, you’re going to want well-fed, happy gut bugs. Soluble fiber helps ensure that happens.

Ok, now you just how important a healthy gut is in overcoming fatigue.

Now, I want to hear from you!

How has a leaky gut impacted your energy? What did you do to improve your gut function?

Do you need help improving your fatigue?

Want to know more than your doctor about fatigue? Click here for more info on how to create a fatigue-free body!

Originally published at Fatigue to Flourish.