Intestinal Permeability: Clinical Unwinding of Leaky Gut

How do we address the treatment of intestinal permeability?  Clinical unwinding of leaky gut.  Is diet important in the treatment of leaky gut?  Vitamin D and Leaky Gut

This is part 5 of a 5-part series on Intestinal Permeability (Leaky Gut)

Main points of this issue:

  • Leaky gut is a condition that responds well to dietary modification and targeted nutritional supplements
  • Our leaky gut treatment protocol is an aggressive and complete program designed to break the vicious cycle of leaky gut
  • This protocol consists of a restricted dietary program and nutritional supplements that have been shown in the literature to reduce intestinal inflammation and repair the intestinal lining
  • This protocol may need to be conducted for an extended period of time for more progressed cases, or for cases of systemic inflammation or autoimmunity
  • The length of time required to make improvement in this condition depends on the mechanisms that are causing the leaky gut
  • There will be some people that will have chronic leaky gut for the rest of their life, such as severe autoimmune patients, or systemic inflammatory conditions
  • The nitric oxide synthase system must be addressed in the treatment of leaky gut
  • The glutathione recycling system must be addressed in the treatment of leaky gut
  • Vitamin D supplementation is important in the treatment of leaky gut

Leaky Gut Treatment Protocol

The treatment of leaky gut includes an aggressive and complete program designed to break the vicious cycle of leaky gut. This consists of a restricted dietary regimen and nutritional supplements that have been shown to help reduce intestinal inflammation and help repair the intestinal lining. This dietary program may need to be conducted for an extended period of time for more progressed cases, depending on the factors involved in promoting leaky gut. It can also be conducted for as little as a few days for quick recovery after exposure to intestinal food sensitivities.

Length of Program

  • Average leaky gut program: 10 days
  • Moderate leaky gut program: 20 days
  • Severe leaky gut program: 30-90 days
  • Chronic leaky gut program: as needed
  • Acute repair program: 3 days

One of the things that will create variables for how long this will take are the mechanisms involved that are causing the leaky gut. If you are still consuming alcohol or consuming inflammatory foods or have hormonal deficiencies or have blood sugar issues, this will take longer to correct. There will be some people that will have chronic leaky gut for the rest of their life, such as severe autoimmune patients and systemic inflammatory conditions.

Foods to Avoid

  • Sugars: including corn syrup, high fructose corn syrup, molasses, honey, chocolate candy, etc.
  • High glycemic fruits: watermelon, mango, pineapple, raisins and canned fruit
  • Grains: including gluten, wheat, oats, rice, barley, buckwheat, soy, corn, wheat germ, spelt, amaranth, kamut, millet, and quinoa, etc.
  • Gluten-containing compounds: including processed salad dressings, ketchup, soy sauce, barbecue sauce, condiments, modified starches, etc.
  • Dairy: including milk, whey, eggs, cheeses, creams, and mayonnaise, etc.
  • Soy: including soy milk, soy sauce, soy protein, etc.
  • Alcohol: including beer, wine, sake, cognac, liquors, etc.
  • Lectins: including nuts, beans, soy, potatoes, tomato, eggplant, pepper, peanut oil, soy oil, etc.
  • Coffee
  • Processed foods
  • Canned foods

Foods to Eat

  • Most vegetables (except tomato, potatoes and mushrooms): including asparagus, spinach, lettuce, broccoli, beets, cauliflower, carrots, celery artichokes, garlic, onions, zucchini, squash, rhubarb, cucumbers, turnips, watercress, etc.
  • Fermented foods: including sauerkraut, kimchi, pickled ginger, mixed pickle, coconut yogurt, kombucha tea, etc.
  • Meats: including fish, chicken, beef, lamb, organ meats, etc.
  • Low glycemic foods: apricot, plum apple, peach, pear, cherries, berries, etc.
  • Coconut: including coconut oil, coconut bitter, coconut milk, etc.
  • Herbal teas
  • Olives and olive oil

Avoid Gluten

It is important to avoid gluten if you have intestinal permeability. Once intestinal permeability develops, gluten sensitivity will develop in almost all cases. Gluten sensitivity will also promote intestinal permeability by activating zonulin (the protein that binds the epithelial cells together). Gluten has been shown to activate the zonulin system directly and continue to promote leaky gut.

“Gliadin binds to chemokine receptor CXCR3 and leads to MyD88-dependent zonulin release and increased intestinal permeability.”1

Key Nutritional Supplements in the Treatment of Leaky Gut Syndrome

When it comes to the treatment of leaky gut, there are two critical systems that need to be addressed:

  • The Nitric Oxide Synthase system
  • The Glutathione Recycling system

The Role of the Nitric Oxide System in Leaky Gut Syndrome

When you look at the nitric oxide system, there are 3 different forms of nitric oxide

  • nNOS
  • eNOS
  • iNOS

Forms of Nitric Oxide Synthase:


  • optimizes neuronal synapses
  • protects the neurons


  • helps tissue recover and regenerate
  • dissolves endothelium plaques
  • dilates blood vessels


  • Promotes tissue destruction
  • Promotes inflammation
  • Promotes AI attack

People that have autoimmunity have poor eNOS and nNOS and very high iNOS, which means they are inflamed but cannot get blood flow or neurologic activity going. When people have nitric oxide system dysfunction, they end up with breakdown of their intestinal barrier.

“iNOS up-regulation and oxidation/nitration of intestinal cytoskeletal proteins, promotes intestinal leakiness.”2

Large amounts of iNOS can increase gut permeability, induce apoptosis and stimulate intestinal secretion.”3

It is known that the overproduction of iNOS is related to intestinal destruction and inflammation. iNOS inhibitors should be considered as potential anti-inflammatory agents for intestinal injury.”4

One of the goals of treatment of intestinal permeability is to provide compounds that are used to support the expression of eNOS and nNOS, while dampening the expression of iNOS.

Compounds that have been shown to modulate the Nitric Oxide System

  • Adeniosine
  • Huperzine A
  • Vinpocetine
  • L-alpha-glycerylphosphosphorylcholine
  • Alpha-ketogluteric acid (AKG)
  • Xanthinol niacinate
  • L-acetylcarnitine (LAC)

The Role of the Glutathione Recycling System in Leaky Gut Syndrome

Glutathione is the main antioxidant that protects cellular mitochondria. Glutathione exists in reduced (GSH) and oxidized (GSSG) states. GSH (reduced glutathione) becomes GSSG (oxidized glutathione) by an enzyme called glutathione peroxidase. GSH can be regenerated from GSSG by the enzyme glutathione reductase. As long as these enzymes are working efficiently, your body is able to maintain this glutathione recycling system and you are fine. When this enzyme system fails, you get activation of iNOS and autoimmunity. The ability to activate these enzymes is critical for autoimmunity.

You dont get leakiness of gut until glutathione stores are depleted

“Glutathione depletion aggravated ileal inflammation after infection.”
“Glutathione is suggested to play an important role in gut barrier function and prevention of intestinal inflammation.”
“Intestinal barrier destruction occurs once glutathione is depleted.”5

In other words, if your glutathione levels are healthy, you will not get intestinal destruction.

“A recent study investigated the role of reactive oxygen species (ROS) modulation with intestinal mucosal permeability damage.”
“Treatment with glutathione precursors prevented the MTX (methotrexate)-induced ROS production and the increase of paracellular permeability.”6

“The researchers concluded that data support the hypothesis that the GSH antioxidant system plays a crucial role in gut barrier protection.”7

If you look at the literature, there are several compounds that help raise intracellular glutathione, activate the glutathione peroxidase and reductase enzymes, and make this process work more efficiently.

Compounds that have been shown to modulate the Glutathione Recycling System

  • Cordyceps: found to raise intracellular RBC glutathione levels by 300% within minutes and has a powerful effect on the enzymes that increase glutathione
  • Centella asiatica
  • Silybum marianum
  • N-acetyl-cysteine
  • Alpha lipoic acid
  • L-glutamine
  • Selenium

Vitamin D and Leaky Gut

Dont forget about the importance of vitamin D for intestinal permeability and autoimmunity:

“There is growing appreciation of the importance of the pleiotropic hormone vitamin D in the development of tolerance, immune system defenses, and epithelial barrier integrity.”8

“These observations suggest that vitamin D plays a critical role in mucosal barrier homeostasis by preserving the integrity of junction complexes and the healing capacity of the colonic epithelium.9

Content provided by Datis Kharrazian, D.C., Breaking the Complex Web of Leaky Gut Syndrome, 2/10/11

1. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology. 2008 Jul;135(1):194-204.e3
2. Nitric oxide-mediated intestinal injury is required for alcohol-induced gut leakiness and liver damage. Alcohol Clin Exp Res. 2009 Jul;33(7):1220-30. Epub 2009 Apr 9
3. Targeting nitric oxide in the GI tract. Curr Opin Investing Drug. 2004 May;5(5):529-36
4. iNOS expression in oral and gastrointestinal tract mucosa. Dig Dis Sci. 2008 Jun;53(6):1437-42
5. Intestinal barrier function in response to abundant or depleted mucosal glutathione in Salmonella-infected rats. BMC Physiol. 2009 Apr 17:9:6
6. Oxidative stress and enhanced paracellular permeability in the small intestine of methotrexate treated rats. Cancer Chemother Pharmacol. 2010 May;65(6):1117-2
7. The role of the glutathione antioxidant system in gut barrier failure in a rodent model of experimental necrotizing enterocolitis. Surgery. 2004 Sep;136(3):557-66
8. Potential mechanisms for the hypothesized link between sunshine, vitamin D, and food allergy in children. J Allergy Clin Immunol. 2010 Aug;126 (2):217-22
9. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol. 2008 Jan; 294(1):G208-16