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Glutamine Supplementation & Gut Health

Glutamine supplement

Glutamine plays an integral role in gut health. Around 30% of the glutamine that the body produces goes to maintaining and fuelling processes in the gut.

What is Glutamine?

Glutamine is the most abundant amino acid in the human body. It is often considered conditionally essential, meaning that our bodies can make it endogenously. Although, there may be times where we must get it from food.

Intracellular concentrations of glutamine can be depleted when the body is under a significant amount of stress such trauma or sepsis. 

During these times, the body may not be able to produce enough glutamine to keep up with the increased requirements by intestinal, renal, and immune cells. When usage of glutamine exceeds the endogenous glutamine production, it is then considered an essential nutrient.

Glutamine & Its Role in The Gut

Effects of L glutamine on the gut

Glutamine has many roles in the body but it is particularly known for being the predominant fuel source in the small and large intestines. 

It is necessary for maintenance of the gut including keeping the gut villi healthy and maintaining the integrity of the gut wall. 

Depletion of glutamine results in several disturbances to the gut.

Villous Atrophy

Villous atrophy is when the villi in the small intestine erode away. The villi are microscopic, finger-like projections that are on the walls of the small intestine. Their role is to increase the surface area of the intestine to allow nutrients to be absorbed by the body as food passes through. 

Losing villi to villous atrophy can result in serious nutritional deficiencies. 

Villous atrophy is seen in untreated celiac disease.

Impaired Cell Replication in The Intestinal Lumen 

Glutamine promotes enterocyte proliferation and is important for maintaining the single cell layer of epithelial cells in the gut lining. 

When glutamine levels are low, the signalling pathways that tell cells in the gut lining to replicate are hindered. This results in lower levels of cell proliferation. 

If cell degradation and proliferation are not occurring in harmony and maintaining homeostasis, this can lead to decreases in the integrity of the gut wall. 

Increased Intestinal Permeability or “Leaky Gut”

Glutamine is also essential for regulating the tight junction proteins between cells in the gut lining. 

These tight junctions are responsible for preventing pathogens and toxins from entering the intestinal lumen and circulatory system.  

Typically, these junctions are dynamic and do not maintain a static structure. This is to allow certain things to freely pass through the intestinal wall.

But this dynamic nature is tightly regulated. 

However, when glutamine levels are low the regulation of the intestinal permeability by the tight junction proteins is disturbed. Leading to a general increase in intestinal permeability that may allow unwanted things to pass through the intestinal wall. 

You may have heard this condition referred to as leaky gut.

Leaky gut is a term mostly used by practitioners of alternative medicine. The leaky gut theory proposes that a porous bowel lining can lead to many issues with digestion, immunity, and disease states.

Although current research is conflicted on the correlation between increased intestinal permeability and specific health outcomes. 

What affects intestinal permeability and how an increased intestinal permeability affects human health is still under investigation.

We do however know that certain disease states and stressors on the body are linked to increased intestinal permeability such as:

  • Inflammatory bowel disease 
  • Gut infections 
  • Coeliac disease
  • Chemotherapy
  • Radiotherapy to the abdomen
  • Immunosuppressants
  • HIV/AIDS
  • Cystic fibrosis
  • Sepsis
  • Complicated surgery 
  • IBS-D

It is unclear how and if glutamine availability plays a role here. 

But there is some interest in glutamine supplementation and its potential effects on improving gut health in these circumstances by regulating the tight junction proteins. 

Evidence also indicates that glutamine has an anti-inflammatory property. It influences a number of inflammatory signaling pathways in the gut which has further strengthened researchers’ interest in the amino acid. Particularly in relation to conditions such as inflammatory bowel disease. 

Increased intestinal permeability

Glutamine Supplementation & Intestinal Conditions – The Research 

Crohn’s Disease & Glutamine

Patients with Crohn’s disease, a subtype of inflammatory bowel disease, have been shown to have lower levels of glutamine in their blood and within their cells. 

This led to the hypothesis that glutamine supplementation would improve clinical outcomes for people with Crohn’s.

Only a limited number of studies have been done in humans to test this hypothesis and with mixed results. 

In a randomized controlled trial, Benjamin et al. reported that glutamine supplementation (0.5 g/kg BW; 2 months) in patients with Crohn’s disease reduced intestinal permeability.

However, a number of studies did not observe any improved outcomes from glutamine supplementation.

IBS & Glutamine

One randomised control trial looking at glutamine supplementation for people experiencing diarrhea specific irritable bowel syndrome (IBS-D) found that it reduced symptoms. 

This was an 8-week-long trial made up of participants with IBS-D following an enteric infection.

IBS-D has been correlated with hyperpermeability of the gut which can be caused by a gut infection. So it makes sense why glutamine may assist with IBS-D symptoms considering it can help reduce gut permeability. 

Chemotherapy

There is some research to suggest that glutamine supplementation can improve mucositis post-chemotherapy in cancer patients. 

Glutamine For Athletes to Reduce Gastrointestinal Issues

Marathon Runner

Gastrointestinal issues (GI) and discomfort are frequently reported amongst athletes particularly in long-distance endurance events. 

Common symptoms related to exercise include nausea, vomiting, abdominal cramps and the urge to have a bowel movement.

Although the reason why these symptoms occur in long-distance athletes is not fully understood. It has been proposed that it may be to do with increased intestinal permeability caused by exercise. 

This is where bacterial compounds are able to cross the intestinal cell lining and trigger an inflammatory response. 

Lipopolysaccharide (LPS) endotoxins are found in large quantities in the human gut. Increased circulating LPS levels in athletes have been found to be associated with gut symptoms including nausea, vomiting, and diarrhea.

Increased permeability or circulating endotoxin could also impact on physical performance or delay recovery. 

Once again, glutamine supplementation is of interest due to its role in maintaining tight cell junctions and potentially preventing or reversing increases in intestinal permeability. 

Research in the athletic population has indicated that acute oral glutamine consumption attenuates GI permeability relative to placebo. This even occurs at lower doses of 0.25 g per kilogram bodyweight.

Although larger doses have been seen in the literature. Doses up to almost 1g per kilo bodyweight daily may be more effective. 

However, it remains unclear if this will lead to reductions in gastrointestinal symptoms. 

It has also been suggested by Jamie Pugh, a researcher in glutamine supplementation, that glutamine supplementation can cause the body’s production of glutamine to down-regulate.

This could potentially lead to a reliance on supplementation but the long term effects are not known.

Summary

Glutamines’ role in gut health is a complicated one. It does appear that glutamine is important for the maintenance of the gut, including the health of the villi and intestinal wall. 

Typically, the body creates enough glutamine to meet its needs. However, when the body is in a stressed state, glutamine usage may be greater than production. This can lead to an array of irregularities in the maintenance of the gut.

It isn’t exactly clear how glutamine supplementation assists with gut related disorders.

But its ability to regulate gut permeability makes it an interesting area of research. Especially when it comes to disorders that are linked with gut hyperpermeability. 

Although some studies showed favorable effects, the clinical efficacy of glutamine supplementation in intestinal diseases remains a controversial issue.

Similarly, managing gastrointestinal distress in athletes during events through glutamine supplementation is still an emerging area of research. 

Athletes competing in endurance events may benefit from acute glutamine supplementation prior to exercise in order to maintain gastrointestinal integrity. But more research is required.

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