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Considering Glutamine for Your Gut? Read This...

Glutamine is a conditionally essential amino acid. It is believed to be helpful in the treatment of leaky gut, a complication of Crohn’s disease. A number of studies also show that glutamine levels are reduced in Crohn’s disease even as the body’s demand for the amino acid increases. Preliminary studies indicate that glutamine can lower inflammation and promote healing in the gastrointestinal tract. However, most human studies fail to find any clinical benefits for giving glutamine to patients with Crohn’s disease. Why is glutamine supplementation ineffective when there are good indications that it should work? Read on to find out.
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The Need for Glutamine

Glutamine is the most abundant free amino acid found in the blood.

Although it is not classified as an essential amino acid, it can be conditionally essential during periods of stress including physical stress due to intensive exercise as well as long-term hospital admission and surgery.

Other conditions that may lower the body’s glutamine levels and/or increase its glutamine need include gastrointestinal disorders such as Crohn’s disease.

Glutamine is mostly produced in the muscles. The liver also produces a small amount of the amino acid but it mostly serves as the clearance site for the glutamine released into the gut.

The brain and the lungs hold the highest amount of glutamine in the body and they release this amino acid in small amounts.

Most of the glutamine found in the body is used up in the intestines. The cells of the intestines utilize glutamine to sustain their growth and functions. In fact, glutamine has been shown to protect the lining of the gastrointestinal tract.

Other cells that need glutamine include cells of the immune system and kidney cells.

Major Roles of Glutamine in the Body
  • Protein synthesis – Glutamine is one of the 20 amino acids used to synthesize the various proteins of the body
  • Energy source – Cells need glutamine to produce energy almost as much as they need glucose
  • Source of carbon and nitrogen – Glutamine donates carbon to the citric acid cycle and nitrogen for the synthesis of purines
  • Regulator of acid-base balance – Glutamine can help alkalinize the kidneys by releasing ammonium. In the blood, glutamine serves as a vehicle for ammonia, thereby, serving as a non-toxic carrier of a toxic compound

Glutamine holds the distinction of being one of the few amino acids that can cross into the brain. In the brain, it is used to synthesize certain neurotransmitters.

The muscle also holds a rich source of glutamine. For its role in muscle functions, bodybuilders usually take L-glutamine supplements regularly.

Foods rich in L-glutamine include fish, beef, chicken eggs, milk and dairy products, beans, spinach, wheat and cabbage.

Glutamine in the Gastrointestinal Tract

There is good evidence suggesting that people with inflammatory bowel disease such as Crohn’s disease do not produce enough glutamine. Low glutamine level in Crohn’s disease is further worsened by the increased need for this anti-stress amino acid.

More specifically, glutamine is believed to increase cell differentiation and improve gut barrier function.

This means that glutamine should promote healing in the inflamed sites of the gastrointestinal tract damaged by Crohn’s disease.

By promoting cell differentiation, glutamine speeds up the turnover of the cells of the gastrointestinal tract.

In addition, glutamine can improve the functional integrity of the gastrointestinal mucosa. This means that the amino acid plugs the gaps in the mucosal surface of the gut and prevents bacteria and other irritants from causing more damage in the gastrointestinal tract.

Leaky Gut Syndrome

Leaky gut is the common name given to a condition of increased intestinal permeability.

Basically, it means that the gaps in between the epithelial cells of the intestine have become wide enough to allow the passage of large macromolecules, undigested foods, toxins and bacteria.

The entry of such substances into systemic circulation directly stimulates the immune system to react in order to deactivate them in the body. Such immune reaction can be widespread and exaggerated enough to cause damage to different organs in the body.

Leaky gut is believed to be involved in the presentations of following chronic diseases:

  • inflammatory bowel disease such as Crohn’s disease and ulcerative colitis
  • type 2 diabetes
  • asthma
  • autism
  • allergies
  • systemic inflammatory response syndrome

In the case of Crohn’s disease, the inflammation in the intestines is believed to cause the widening of the junctions (TJs or tight junctions) between the cells of the intestinal lining.

The leakage of unwanted substances into blood circulation may, therefore, stimulate immune reactions in other parts of the body. Specifically, the immune system develops antibodies against these unwanted substances and then mounts an attack against them.

The leakage and the immune response may cause low-grade fever and stomach pain in affected individuals.

Although leaky gut syndrome is still not fully understood, researchers have proposed certain solutions based on current information about the condition. Generally, they believe that natural anti-inflammatory and antioxidant agents such as glutamine, cysteine and zinc can help the intestine recover.

A Summary of Background Studies on Glutamine and Crohn’s Disease

A 1989 study published in the journal, Gastroenterology, identified that patients with Crohn’s disease have increased intestinal permeability compared to their healthy relatives and the general population. This is believed to be partly caused or worsened by low plasma glutamine level.

In a 1990 study published in the journal, Nutrition Review, the researchers identified that glutamine is a conditionally essential amino acid in Crohn’s disease.

In addition, they also confirmed that the utilization of the amino acid is increased in patients with this disease. The diseased intestinal mucosa is believed to place a high demand on glutamine as the body tries to heal the damage done to the intestine.

With such increased demand, glutamine intake needs to rise in order to avoid glutamine deficiency.

A 2006 study published in the journal, Digestive Diseases and Sciences, examined the effect of glutamine supplementation on animals induced with ileitis, a disorder resembling Crohn’s disease.

The researchers found that glutamine improved ileitis and increased the production of the antioxidant compound known as glutathione.

A similar study published in 1988 in the journal, Parenteral Enteral Nutrition, found that glutamine supplementation can reduce inflammation and disease activity.

A 2005 study published in the British Journal of Surgery also established that glutamine supplementation can prevent the transfer of infectious bacteria from diseased parts of the gastrointestinal tract to new sites.

This can significantly reduce gastrointestinal inflammation in Crohn’s disease.

However, glutamine has more specific anti-inflammatory effects. A 2003 study published in the journal, Clinical Nutrition, established that glutamine can reduce the production of pro-inflammatory cytokines (the interleukins, IL-6 and IL-8) while increasing the release of anti-inflammatory cytokines (IL-10) in the mucosal surface of the intestines.

Additional support for the anti-inflammatory effects of glutamine comes from a 2004 study published in the same journal.

Does Glutamine Help Crohn’s Disease?

With such body of scientific work pointing to the clinical benefits of glutamine supplementation in the treatment of Crohn’s disease, one may be tempted to recommend glutamine for patients with Crohn’s disease without reservation.

However, most of the positive studies on glutamine supplementation in Crohn’s disease were preliminary, in vitro or involved animal models. So, how does glutamine perform in human studies?

Active Crohn’s Disease

A 2005 study published in the European Journal of Clinical Nutrition investigated the benefits of glutamine supplementation in 24 patients with active inflammatory bowel disease.

Nineteen of the recruited patients had Crohn’s disease while the other 5 had ulcerative colitis.

Along with the usual anti-inflammatory therapy and total parenteral nutrition, half of the patients received L-alanine-L-glutamine while the other half did not.

The results of the study showed that plasma glutamine levels did not significantly differ between the 2 groups. In addition, intestinal permeability did not change with glutamine supplementation. In fact, the results showed that glutamine did not affect disease activity, nutritional changes or inflammatory status.

Therefore, the researchers concluded that glutamine supplementation offered no clinical benefits for patients with active inflammatory bowel disease

Crohn’s Disease Patients in Remission

A 2006 study published in the journal, Clinical Nutrition, investigated the possible benefits of glutamine supplementation for Crohn’s disease patients in remission.

The researchers recruited 6 adult patients and matched them with 6 healthy adults. The participants were given leucine and glutamine by intravenous infusion but none of them received additional nutritional supplement or anti-inflammatory drug.

The results of the study showed that at least while in remission, patients with Crohn’s disease utilized glutamine normally.

There was no difference in the production, uptake, oxidation and metabolism of glutamine between the control group and the patients with Crohn’s disease.

The study demonstrates that Crohn’s disease patients in remission do not need glutamine supplements.

In Children with Crohn’s Disease

A 2000 study published in the Journal of Pediatric Gastroenterology and Nutrition investigated the benefits of glutamine supplementation in children with Crohn’s disease.

For this study, the researchers recruited 18 children with active Crohn’s disease. They were randomly assigned to either a polymeric diet with low glutamine content or a glutamine-rich polymeric diet. Besides their glutamine contents, the 2 diets had similar amounts of calories and nitrogen composition.

After 4 weeks, the results of the study showed that there was no difference in rate of remission, weight and platelet count between the 2 groups.

In fact, the group that received the low-glutamine diet scored higher on the pediatric Crohn’s disease activity index (PCDAI) than the high-glutamine group.

These results suggest that glutamine supplementation is not needed in the management of Crohn’s disease in children. In fact, it may worsen the disease in some patients.

In addition, the researchers also concluded that the positive results obtained with glutamine supplementation in animal studies and disorders similar to Crohn’s disease should not be blindly applied to the management of Crohn’s disease.

Long-term Supplementation of Glutamine

The authors of a 1999 paper published in the Journal of Parenteral and Enteral Nutrition studied the effects of glutamine supplementation on intestinal hyperpermeability (leaky gut) in a group of patients with Crohn’s disease.

The researchers recruited 14 patients with leaky gut syndrome. In addition to their usual treatment, 7 of them received 7 g of oral glutamine 3 times daily while the other 7 received glycine in the same dosage.

Treatment and supplementation continued for 4 weeks before the participants were evaluated.

The results of the study showed that neither glutamine nor glycine improved intestinal permeability.

In addition, glutamine supplementation did not affect plasma glutamine, plasma glutamate or plasma ammonium levels. The amino acid also did not improve the patients’ nutritional status or Crohn’s disease activity index.

The researchers concluded that glutamine supplementation did not restore impaired intestinal permeability. Therefore, its use in the management of Crohn’s disease is questionable.

Reasons for Glutamine Failure

In response to the results of the previous study, a group of clinicians and researchers published a letter to the editor of the journal explaining their own experiences with glutamine supplementation in Crohn’s disease.

In their illuminating piece, the clinicians confirmed that even though polymeric enteral nutrition was effective in the treatment of leaky gut syndrome, the addition of glutamine did not improved its efficacy.

In their experience, the benefits documented for glutamine supplementation in similar catabolic states did not carry over to Crohn’s disease.

The similar catabolic conditions mentioned include post-surgery stress, chemotherapy and bone marrow transplantation. Like Crohn’s disease, these conditions increase the need for glutamine as the body tries to heal itself.

The authors of the paper agreed that the reason for the ineffectiveness of glutamine in the management of Crohn’s disease was unknown. But they provided some possible explanations.

T Cell Involvement

A number of studies have identified increased T cell activation as one of the features of Crohn’s disease.

Patients with Crohn’s disease usually have elevated levels of T cells. This family of immune cells triggers the release of pro-inflammatory cytokines in the gastrointestinal tract. Unfortunately, glutamine is also known to enhance T cell function.

Therefore, glutamine may increase inflammatory activity in Crohn’s disease.

In fact, a 1997 study published in the journal, Diseases of the Colon and Rectum, highlighted this link between glutamine and inflammation in the gastrointestinal tract.

In that study, researchers induced colitis in 3 groups of rats and then gave them different doses of glutamine. The results showed that the rats that received the highest dose of glutamine had the worst intestinal inflammation.

Nitric Oxide

Yet another suggested reason for the failure of glutamine in reducing inflammation in Crohn’s disease involves nitric oxide.

In the gut, glutamine is converted to citrulline which is then converted to arginine. Arginine is then used in the production of nitric oxide. Therefore, glutamine serves as a precursor of nitric oxide.

Unfortunately, high levels of nitric oxide in the gut have been shown to worsen the tissue damage and inflammation experienced in Crohn’s disease and ulcerative colitis.





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