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How To Use Leaky Gut Supplements To Target Inflammation

The Connection Between Leaky Gut and Inflammation

Many people consider leaky gut syndrome, a common term for when holes form in the lining of the small intestine, a mere digestive disorder. However, leaky gut may be less about digestion and more likely a result of long-term inflammation promoted by chronic illness, excess weight, poor dietary choices 1, extreme exercise (looking at you, marathon runners and triathletes) 2, and too many non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen 3 4. However, leaky gut supplements may be able to help.

As I’ve emphasized in my book, Healthy Gut Healthy You, the digestive system is probably the main source of inflammation in the body 5. Ergo, the best way to treat and prevent leaky gut may be reducing overall inflammation through a combination of supplements, diet, stress reduction techniques, and moderate exercise.

In this article, we’ll explore the most well-researched supplements for leaky gut, including l-glutamine, probiotics, colostrum, zinc, and zeolite. We’ll also look at other supplements and therapies that can reduce the burden of gut inflammation.

Leaky gut supplements: A woman pointing to a digestive system model

What Is Leaky Gut?

Also called intestinal permeability or gut hyper-permeability, leaky gut syndrome is what happens when the tight junctions — membranes that lock the cells lining your small intestine together to keep its contents inside — come loose. As a result, undigested food particles and bacteria can sneak past the intestinal wall and get into the bloodstream, where they don’t belong.

Leaky gut supplements: Leaky gut syndrome illustration

When this happens, foreign molecules in the blood trigger an immune response (inflammation) and an increase in zonulin, a protein thought to guard the small intestine against invasive organisms 6 7. In fact, high levels of zonulin in the small intestine are considered a sign of leaky gut and may be associated with an increased risk of autoimmunity 8.

The longer leaky gut goes on, the more likely it is to contribute to a vicious inflammatory cycle that can affect other organs throughout the body, giving rise to more inflammation and worsening intestinal permeability 9.

What Causes Leaky Gut?

Healthcare professionals have long assumed that leaky gut goes hand-in-hand with digestive issues. But new, high-quality research that analyzed many studies of intestinal permeability found that digestive symptoms were not actually correlated with leaky gut in most adults 10.

This research found that the issues most strongly associated with leaky gut are 11:

  • Inflammation
  • Metabolic issues
    • High concentrations of lipids (triglycerides or cholesterol) in the blood
    • High blood sugar
    • Overweight/obesity
    • Metabolic syndrome
  • Chronic conditions, such as:
    • Liver disease
    • Diabetes
    • Kidney disease
    • Polycystic ovarian syndrome (PCOS)
    • Celiac disease and other autoimmune diseases, such as inflammatory bowel disease (IBD)
  • Eating a Western diet (low in nutrients but high in sugar, processed ingredients, and alcohol) that supports the wrong kinds of gut bacteria.
leaky gut supplements: boxes listing the causes of leaky gut

The study also found that, unless you have a diagnosable condition inflaming your GI tract (think IBD, IBS with diarrhea, dysbiosis, disease-related diarrhea, or indigestion), symptoms like bloating, cramping, pain, heartburn, reflux, nausea, and gas are probably not signs of leaky gut 12.

In other words, leaky gut may be a characteristic of chronic disease in general, rather than being specifically linked to gut conditions. However, chronic digestive issues may give rise to chronic inflammation, which is highly correlated with leaky gut 13.

Other studies have found that an overuse of NSAIDs, like ibuprofen 14 15, and very long, intense exercise that raises body temperature to 102.2 F 16 may directly cause leaky gut.

Overall, the above risk factors have an inflammatory effect, which appears to be closely linked to developing leaky gut.

How Do You Know If You Have Leaky Gut?

If you suspect you may be at risk of developing leaky gut, you can ask a healthcare professional about the dual sugar test and serum zonulin test 17. There is no “gold standard” of testing for leaky gut 18 19, but a combination of these two tests could provide clinically useful information.

1. The dual sugar test: Lactulose in your urine signals that your gut is probably leaky. 

  • This test involves fasting overnight and then drinking a mixture of two types of sugars — often, mannitol and lactulose — before collecting your urine.
  • If your intestinal lining is healthy, the mannitol should be absorbed by the small intestine and later appear in your urine.
  • The lactulose, which is larger, should stay inside the intestine and never reach the urine.
  • The effectiveness of this test is limited by the uncertainty of normal values and a lack of standardization 20. Furthermore, small intestinal bacterial overgrowth (SIBO) may falsify the results 21, so combining this test with serum zonulin may strengthen its conclusions.

2. Serum zonulin: High zonulin may be a good clinical indicator of leaky gut, especially when measured in blood rather than stool 22.

  • Zonulin levels also rise with overweight/obesity, high blood pressure, high blood sugar, high triglycerides, high cholesterol, and autoimmunity 23, so it’s harder to be certain that elevated levels specifically indicate leaky gut.
  • This is another reason why combining serum zonulin with the dual sugar test may be useful.

Unfortunately, leaky gut testing is time-consuming, imperfect, and expensive, and I don’t recommend it. That said, if you have one or more of the factors that may contribute to leaky gut, you could choose to take simple steps, including certain supplements and lifestyle changes, to lower inflammation and heal your gut lining.

Leaky Gut Supplements

The following supplements have the most high-quality research examining their potential to directly heal leaky gut:

L-glutamine

Multiple studies have found that L-glutamine supplements normalize gut wall integrity in the following types of people:

  • Patients with leaky gut and diarrhea-predominant IBS 24
  • Active men who exercise hard in the heat 25
  • Critically ill patients 26
  • Patients on long-term radiation therapy 27
  • Patients with HIV/AIDS 28
  • Patients with Crohn’s disease 29

Although bone broth hasn’t been clinically researched much, it is a whole-food source for L-glutamine, other amino acids, and minerals that may benefit the gut lining 30. Given its lower concentrations of healing properties, bone broth may also pack a lighter punch than supplements.

Probiotics

A large body of research shows that probiotics may be effective at reducing zonulin and preventing or repairing leaky gut.

  • A recent high-quality study found that probiotic supplements reduced serum zonulin, an indicator of leaky gut 31.
  • Many recent, high-quality clinical studies found various probiotic microorganisms, such as Bifidobacterium longum, B. animalis, and Lactobacillus rhamnosus, restored intestinal barrier function and reduced intestinal permeability in IBS patients, overweight and obese adults, and colon cancer patients 32 33 34 35 36 37.
  • For marathon runners and triathletes, another study found that a probiotic strain called Lactobacillus salivarus, which is native to human intestines, protected against exercise-induced leaky gut 38.
  • And if you prefer to get your probiotics from food, another study found that supplementing with kefir improved serum zonulin levels in overweight adults 39. Keep in mind that the probiotics in food come in smaller doses than in supplements and may be less therapeutic.

However, there is some controversy regarding probiotics and leaky gut. A number of other high-quality studies found that probiotics did not regularly improve intestinal permeability 40 41 42 43 44 45 46 47, even when the probiotics helped with SIBO and related symptoms 48 or reduced GI symptoms 49.

Unfortunately, leaky gut research is confounded by a number of factors, primarily the lack of quality ways to measure its occurrence or severity. However, most research points to leaky gut as a result of inflammation—much of which starts in the gut—and probiotics have repeatedly been found to reduce gut inflammation.

So, as long as the probiotics you use are high in quality and contain well-studied strains of good bacteria, taking them along with a healthy diet and other anti-inflammatory lifestyle approaches will likely help reduce inflammation and help to improve the integrity of your gut wall.

Colostrum

Research shows that bovine colostrum (the first milk produced after a calf is born) may improve leaky gut and reduce zonulin levels in competitive athletes 50 51.

Zinc

Low-dose zinc supplementation may improve leaky gut in children with inflamed digestive tracts 52, and zinc carnosine (a mineral-amino acid compound) may increase gut lining strength in active adult men who exercise heavily 53.

Zeolite

Zeolite, a collection of silica-based minerals that naturally come from volcanoes, may improve intestinal wall strength in endurance athletes by reducing zonulin levels 54.

Other Supplements With Anti-Inflammatory Health Benefits

Although the following supplements haven’t been rigorously tested for their direct effects on leaky gut, they have been found in some studies to reduce inflammation and/or support gut healing.

  • Vitamin D 55
  • Digestive enzymes 56 57 58
  • DGL (deglycyrrhizinated licorice root) 59
  • Aloe vera 60
  • Quercetin 61
  • Fish oil 62
  • Immunoglobulins 63
  • Collagen 64

How To Use Lifestyle Changes To Heal Leaky Gut

Leaky gut is a condition that’s very much influenced by your lifestyle choices. While supplements can play an important role in the healing process, don’t overlook the importance of these lifestyle choices:

  • Eat a balanced, nutrient-dense diet low in inflammatory foods, such as the paleo diet. You may need to figure out your best diet by temporarily removing foods that may trigger your immune system, such as gluten, dairy, eggs, FODMAPs, or nuts. Reintroduce these foods one at a time to see if you react to them.
  • Limit sugar, and keep carb intake to whole foods like fruits, vegetables, and grains that your digestive system tolerates well.
  • Exercise regularly but moderately – don’t overdo it.
  • Practice breathing exercises and meditation to reduce stress and support your nervous system.
  • If you have a chronic condition, get help from a healthcare professional who is aware of the roles the gut microbiome and digestive health may play in your condition.

The Bottom Line on Leaky Gut and Inflammation

Overall, leaky gut syndrome seems to both result from and contribute to chronic inflammation. To reduce inflammation and thereby lower your risk for leaky gut, I recommend research-backed leaky gut supplements and incorporating lifestyle changes that support your gut health and immune system.

For help with healing leaky gut, schedule an appointment at the Ruscio Institute for Functional Health.

➕ References

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  2. Pires W, Veneroso CE, Wanner SP, Pacheco DAS, Vaz GC, Amorim FT, Tonoli C, Soares DD, Coimbra CC. Association Between Exercise-Induced Hyperthermia and Intestinal Permeability: A Systematic Review. Sports Med. 2017 Jul;47(7):1389-1403. doi: 10.1007/s40279-016-0654-2. PMID: 27943148.
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  15. Mujagic Z, de Vos P, Boekschoten MV, Govers C, Pieters HH, de Wit NJ, Bron PA, Masclee AA, Troost FJ. The effects of Lactobacillus plantarum on small intestinal barrier function and mucosal gene transcription; a randomized double-blind placebo controlled trial. Sci Rep. 2017 Jan 3;7:40128. doi: 10.1038/srep40128. PMID: 28045137; PMCID: PMC5206730.
  16. Pires W, Veneroso CE, Wanner SP, Pacheco DAS, Vaz GC, Amorim FT, Tonoli C, Soares DD, Coimbra CC. Association Between Exercise-Induced Hyperthermia and Intestinal Permeability: A Systematic Review. Sports Med. 2017 Jul;47(7):1389-1403. doi: 10.1007/s40279-016-0654-2. PMID: 27943148.
  17. Leech B, McIntyre E, Steel A, Sibbritt D. Risk factors associated with intestinal permeability in an adult population: A systematic review. Int J Clin Pract. 2019 Oct;73(10):e13385. doi: 10.1111/ijcp.13385. Epub 2019 Jul 5. PMID: 31243854.
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  30. https://drruscio.com/bone-broth-diet/
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