Leaky Gut: Glutamine May Help Your Leaky Gut

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I have come across L-glutamine a dozen or so times when looking for different methods to heal intestinal permeability or leaky gut and I’m sure if you are reading this you have as well. So when I sat down to write this article I thought it would be a simple dive into the literature to confirm that glutamine is helpful in the healing of leaky gut.

To my surprise the answer to whether glutamine is helpful in healing leaky gut is not so straightforward.

Glutamine & the Gut

Glutamine is an amino acid that has been used to help heal the gut for quite some time. Although it is not technically an essential amino acid (meaning the body can synthesise it) some have argued that it is essential in times of stress when the body fails to synthesise it in the amounts that are needed (1).

Glutamine has been shown to be a major fuel source for enterocytes. These are the cells that line the small intestine and facilitate digestion and absorption into the bloodstream (2).

The tight junctions, as we’ve previously discussed, are found between these enterocyte cells. Together they form the gut barrier that is so important to maintain. One review published in 2013 spoke to the breakdown in this barrier (intestinal permeability/leaky gut) that has been correlated with a number of different diseases including food allergies, inflammatory bowel disease, celiac disease, irritable bowel syndrome and type I diabetes.

The review focused on some major areas that glutamine assists the body.

Tight Junctions – These are incredibly complex junctions that bind the epithelial cells together. They are selectively permeable allowing certain molecules to pass and blocking others. A deficiency on glutamine increases intestinal permeability and impaired cellular proteins. In the glutamine deficient model the addition of glutamine helped to restore the gut barrier.

Gut Immune Function – The gut associated lymphatic tissue, or GALT, secretes a specific antibody in defence against microbial invaders. This antibody known as IgA prevents bacterial adherence to the intestinal mucosa. Under stressful conditions this process can become impaired. The addition of glutamine was shown to improve the production of IgA when it was impaired leading to less bacteria adhering to the intestinal walls.

The authors concluded with some important points on the benefits of glutamine

‘Dietary Gln (glutamine) has been shown to be important for maintenance of the intestinal mucosal barrier by regulating expression of genes and proteins involved in cell proliferation, differentiation and apoptosis, protein turnover, anti-oxidative property, and immunity responses.’

There have been numerous human trials that have explored glutamine supplementation for a range of different diseases. From the information explored above it appears that this single amino acid plays a number of important roles in the body, most notably improving intestinal cell function.

Animal models have shown glutamine to reduce intestinal permeability (4, 5).

The human trials, which we are much more interested in, have mixed results.

A Note Of Caution When Using Glutamine

There have been a number of papers suggesting that glutamine may not be all it’s cracked up to be. One paper notes that although we do have animal studies showing glutamine’s effectiveness on improving intestinal permeability a number of human trials have shown that it has not been effective at all particularly in IBD.

A Cochrane review looked at the trials available for assessing glutamine as an intervention for active Crohn’s disease. They found a few small trials that showed that glutamine was not helpful and concluded that we need larger trials to make a proper assessment.

Pro Glutamine Trials for Leaky Gut

One trial took patients being treated for cancer and assessed the beneficial effects of the addition of 18 grams of glutamine per day on intestinal absorption and intestinal permeability.

They concluded that

‘oral glutamine may be effective in protecting the human intestinal mucosa from chemotherapy induced damage’

A meta-analysis looking at a range of different trials assessing glutamine supplementation in abdominal surgery came to some interesting results. They found that glutamine supplementation in post-abdominal surgery patients

  • Reduced inflammatory markers (c-reactive protein, tumour necrosis factor alpha, interleukin 6)
  • Increased interleukin 2 receptors that bind to interleukin 2 – a messenger molecule that helps regulate immune function.
  • Improved intestinal permeability scores
  • Decreased levels of endotoxin

Glutamine was assessed in patients with Crohn’s disease in remission that still had intestinal permeability or leaky gut. In one group they administered glutamine at a dose of one third of the protein requirements of the patient. This equalled 0.5 grams of glutamine per kilogram of body weight for each patient. For a 70kg person this would equate to 35 grams of glutamine per day. In the ‘placebo’ arm they supplemented with whey protein. In both groups there was improvements in both intestinal permeability and structure (2).

Glutamine Dosages for Leaky Gut

The dosages of glutamine that come in mixed gut healing formulas are much lower than the amounts the trials use. Some products that I have come across have only 1 gram of glutamine per day. From the trials it appears that doses ranging from 10 grams per day all the way up to 35 grams per day have shown effectiveness in reducing and healing leaky gut.

Sound advice would be to work with an experienced clinician and to start on the very low end and to gradually ramp up the dosage to a comfortable range. As with all supplements and herbs be sure to note negative reactions including stomach pain, change in bowel movements, headaches and nausea. If you experience any of these it’s best to stop or reduce your intake until the symptoms resolve.

Mixed Results

It appears that glutamine may or may not be helpful in healing intestinal permeability. Different trials note different results and it can be tough to draw any concrete conclusions.

This may be another great example that outlines how each person is an individual. Some may benefit from an intervention and some may not. There are many experienced clinicians that recommend glutamine to help heal and seal the gut and anecdotal evidence is plentiful. That said it is worth keeping in mind that glutamine may not be the be all and end all that heals your leaky gut. Other approaches may be more suited for your particular situation.

If you’ve had any success or failures using glutamine share your experience. Leave a comment below.

References and Resources

  1. Effect of the route of glutamine supplementation (enteral versus parenteral) on intestinal permeability on surgical intensive care unit patients: A pilot study
  2. Glutamine and Whey Protein Improve Intestinal Permeability and Morphology in Patients with Crohn’s Disease: A Randomized Controlled Trial
  3. Glutamine and intestinal barrier function
  4. Glutamine Supplementation Decreases Intestinal Permeability and Preserves Gut Mucosa Integrity in an Experimental Mouse Model
  5. Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis
  6. Glutamine and Whey Protein Improve Intestinal Permeability and Morphology in Patients with Crohn’s Disease: A Randomized Controlled Trial
  7. Glutamine for induction of remission in Crohn’s disease (Review) 
  8. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial
  9. Effects of glutamine on markers of intestinal inflammatory response and mucosal permeability in abdominal surgery patients: A meta-analysis

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