Zinc Reduces Gut Leakage
3 minutes
difficulty level Advanced
Matthew Messer

Matthew Messer


Although the existence of leaky gut syndrome is still controversial, increased intestinal permeability can be seen in several chronic diseases, which can lead to various problems over time. In order to ensure the health of the intestinal wall, proper immunity is essential, which is unthinkable without zinc - and several studies suggest that supplementing it can help reduce intestinal permeability.

What does leaky gut mean?

Our digestive system is responsible for breaking down food and absorbing nutrients essential for health. Ideally, the intestinal wall is tightly closed, allowing only the nutrients we really need to pass through. However, if for some reason the intestinal wall is damaged - for example, by digestive tract infections, irritating additives or other inflammation - intestinal permeability can increase, allowing bacteria and allergens to enter the bloodstream and stimulate the immune system. (1)

Increased intestinal permeability has been observed in several chronic diseases, (2) though it is debated whether this is their cause or their consequence. In any case, it is clear that maintaining the integrity of the intestinal wall is key and that we need certain micronutrients to do this.

Why is zinc important for the digestive system?

Zinc, along with hundreds of enzymes, is also necessary for the function of our immune cells, so a lack of zinc decreases our immunity and increases inflammation. (3) It is also a building block of certain proteins that make up our tissues, so it is essential for regeneration after infections.

We have already reported in another article that half of patients with inflammatory bowel disease are zinc deficient. (4) This is because frequent diarrhea and complications of gastrointestinal diseases further increase the excretion of zinc from the body, so not only do we take in less, but we also excrete much more. (5)

Zinc is therefore important for preventing infections, regulating inflammatory processes and for proper regeneration, and as these processes also increase our demand, we can easily become deficient.

Zinc can help restore leaky intestinal wall

In a randomized trial in 2015, children with gastroenteritis and diarrhea were treated with oral rehydration fluid, while one group also received 3 mg of zinc. Although this is a very small amount (not even enough to cover the daily intake), it significantly reduced intestinal permeability in the children who received zinc supplementation. (6)

Its effectiveness has been established by a dedicated blood test that detects intestinal permeability from the ratio of plasma lactulose to l-ramnose. (7) Lactulose is a large molecule, very little of which is usually absorbed from the intestine, but if the intestine becomes more permeable, lactulose can be absorbed, which will be visible in the test.

Even this small amount of zinc supplementation helped to reduce intestinal permeability, although the research was done in Australia, not in a developing country, proving zinc supplementation potentially useful in developed countries.

Although zinc did not reduce the duration of diarrhea in this study, a systematic review suggests that it can do so by an average of 20%. (8)

A study published in 2007 tested the effects of zinc supplementation on intestinal permeability in cells, animal models and finally in humans. Here, a form of zinc carnosine was used, which was first shown in cell cultures to enhance cell migration after injury and thus aid regeneration. (9)

They then tested in mice whether, when given non-steroidal anti-inflammatory drugs, which are known to increase intestinal permeability and can damage the small intestinal wall, zinc could prevent the negative effects. As a result of the trial, zinc reduced the damage to the digestive tract caused by the drug, by 38% from a lower dose and by 75% from a higher dose.

Finally, zinc supplementation was tested in healthy humans in a randomized trial. They were also given a non-steroidal anti-inflammatory drug, with the addition of 2x 37.5 mg of zinc carnosine or placebo, depending on the group. Results were measured using the lactulose/ramnose test mentioned above.

In the control group, the rate of intestinal perforation was increased threefold by NSAIDs, while the risk was not significantly increased in people who supplemented with zinc alongside their medication. In addition, none of the zinc supplement group reported feeling digestive discomfort, while several of the other group did.

Zinc therefore reduces heightened intestinal permeability and may promote recovery from inflammation or injury of the digestive tract.


Due to modern diets and agricultural practices, many people do not reach their daily intake of zinc, which is particularly needed for many digestive diseases. If you have a digestive problem, supplementing with zinc and other trace minerals, either separately or in the form of a multivitamin, can be helpful in addition to a proper diet and lifestyle.

  1. Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke JD, Serino M, Tilg H, Watson A, Wells JM. Intestinal permeability--a new target for disease prevention and therapy. BMC Gastroenterol. 2014 Nov 18;14:189. doi: 10.1186/s12876-014-0189-7. PMID: 25407511; PMCID: PMC4253991.
  2. Bradley Leech, Janet Schloss, Amie Steel, Association between increased intestinal permeability and disease: A systematic review, Advances in Integrative Medicine, Volume 6, Issue 1, 2019, Pages 23-34, ISSN 2212-9588, https://doi.org/10.1016/j.aimed.2018.08.003.
  3. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998 Aug;68(2 Suppl):447S-463S. doi: 10.1093/ajcn/68.2.447S. PMID: 9701160.
  4. Zupo R, Sila A, Castellana F, Bringiotti R, Curlo M, De Pergola G, De Nucci S, Giannelli G, Mastronardi M, Sardone R. Prevalence of Zinc Deficiency in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Nutrients. 2022 Sep 29;14(19):4052. doi: 10.3390/nu14194052. PMID: 36235709; PMCID: PMC9572015.
  5. Castillo-Duran C, Vial P, Uauy R. Trace mineral balance during acute diarrhea in infants. J Pediatr. 1988 Sep;113(3):452-7. doi: 10.1016/s0022-3476(88)80627-9. PMID: 3411389.
  6. Tran CD, Hawkes J, Graham RD, Kitchen JL, Symonds EL, Davidson GP, Butler RN. Zinc-fortified oral rehydration solution improved intestinal permeability and small intestinal mucosal recovery. Clin Pediatr (Phila). 2015 Jun;54(7):676-82. doi: 10.1177/0009922814562665. Epub 2014 Dec 16. PMID: 25520366.
  7. Holtz LR, Hoffmann J, Linneman L, He M, Smyrk TC, Liu TC, Shaikh N, Rodriguez C, Dyer RB, Singh RJ, Faubion WA. Rhamnose Is Superior to Mannitol as a Monosaccharide in the Dual Sugar Absorption Test: A Prospective Randomized Study in Children With Treatment-Naïve Celiac Disease. Front Pediatr. 2022 Apr 7;10:874116. doi: 10.3389/fped.2022.874116. PMID: 35463906; PMCID: PMC9021878.
  8. Patel A, Mamtani M, Dibley MJ, Badhoniya N, Kulkarni H. Therapeutic value of zinc supplementation in acute and persistent diarrhea: a systematic review. PLoS One. 2010 Apr 28;5(4):e10386. doi: 10.1371/journal.pone.0010386. PMID: 20442848; PMCID: PMC2860998.
  9. Mahmood A, FitzGerald AJ, Marchbank T, Ntatsaki E, Murray D, Ghosh S, Playford RJ. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut. 2007 Feb;56(2):168-75. doi: 10.1136/gut.2006.099929. Epub 2006 Jun 15. PMID: 16777920; PMCID: PMC1856764.

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