L-Glutamine: Benefits, Gut Health, Side Effects

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Dr. Scott Buesing, N.D. Posted on June 14, 2023

Protein is a necessary part of the human diet. And all proteins are made up of amino acids. Of the amino acids, some are considered essential, while others are non-essential. Essential amino acids must be consumed in the diet since the body cannot make them from other compounds. The body can produce non-essential amino acids from other dietary components.

L-glutamine is a nonessential amino acid that is found in food and is one of the building blocks of protein. However, in some situations where the body is highly stressed, glutamine may become essential as the body can’t produce enough. In these situations, L-glutamine is considered “conditionally essential.” It is worth noting that L-glutamine is the most abundant free-form amino acid found in the human body.

Functions of L-Glutamine

Free L-glutamine has a number of roles in the human body. First, L-glutamine acts as a shuttle for nitrogen. This allows for the normal processing of ammonia in the liver. It also contributes to the synthesis of glutamate, the main excitatory neurotransmitter, although the process is highly regulated.

A number of different cell types, including connective tissue cells, immune system cells, and cells lining the intestinal tract, use glutamine as fuel. This is particularly important in the small intestine, as these cells use glutamine as their primary fuel source. As such, the small intestine uptakes more L-glutamine than any other organ in the body.

Glutamine also plays a number of roles in immune function. Glutamine is needed for the replication of certain white blood cells. It’s also necessary for the production of immune signaling molecules that are critical for a proper immune response. The ability of certain white blood cells to attack or engulf bacteria and other threats to the body also relies on the amino acid.

As a nutrient, L-glutamine even appears to play a role in blood sugar regulation. Additionally, L-glutamine is important for synthesizing connective tissue, which gives it a role in wound healing.

Potential Health-Related Benefits

Here are some of the potential health-related benefits of L-glutamine

Gastrointestinal Health and Leaky Gut

One of the areas where L-glutamine is often touted for its benefits is for gastrointestinal health. As a primary fuel for the cells that line the digestive tract, L-glutamine plays a critical role in maintaining the health of the digestive tract lining. When this lining gets damaged, it can leak, allowing some undigested digestive tract contents to more readily get into the bloodstream. When a patient has increased intestinal permeability or “leaky gut,” the condition can contribute to gastrointestinal symptoms, food sensitivities, autoimmune conditions, depression, and poor mental health, among other problems. When proteins pass through the intestinal lining and get into the bloodstream, they can cause an immune response increasing inflammation throughout the body.

Of interest, research shows that L-glutamine, similar to zinc and probiotics, may help to protect from or restore damage to the intestinal lining. As such, in some cases, L-glutamine may be considered as a part of a protocol for addressing leaky gut in patients. Studies often use one of two forms of L-glutamine, either the isolated amino acid, or alanyl-glutamine, a “dipeptide” containing two amino acids, alanine and glutamine, combined.

Intravenous Nutrition

The first human study exploring L-glutamine to heal leaky gut focused on hospitalized patients requiring intravenous feeding. Typically, the digestive tract becomes leaky with increased permeability if no food is taken by mouth. However, in the study, adding glutamine to an intravenous nutritional formulation maintained the health of the digestive tract, even without regular food intake.

Inflammatory Bowel Disease and Irritable Bowel Syndrome

However, studies in patients with inflammatory bowel disease, often characterized by bloody, loose stools and increased intestinal permeability, are quite mixed. In three smaller studies, L-glutamine was shown to be of no benefit. However, in a recent small trial, L-glutamine did appear to provide benefits in reducing intestinal permeability. It’s possible that, in some cases, the underlying pathology present in patients with inflammatory bowel disease needs to be addressed before the gastrointestinal lining can heal. More and larger studies are needed to establish better if L-glutamine can benefit a subset of inflammatory bowel disease patients.

For patients with irritable bowel syndrome, data suggests that L-glutamine could be of benefit. Irritable bowel syndrome is a common condition characterized by abdominal pain, diarrhea, constipation, or both. Gastrointestinal infections are known to cause increased permeability, likely from the inflammation present during the infection. This can lead to the development of irritable bowel syndrome in susceptible individuals. In one study, L-glutamine “dramatically and safely reduced all major IBS-related endpoints” in patients with irritable bowel syndrome following a gastrointestinal infection, according to the authors.

In a separate small trial of diarrhea-predominant irritable bowel syndrome, glutamine was also potentially helpful. In patients with evidence of a more severe leaky gut, supplementation of L-glutamine increased “tight junction proteins,” proteins related to a decrease in intestinal permeability.

A recent trial explored combining L-glutamine with a low FODMAP diet for irritable bowel syndrome. A low FODMAP diet attempts to remove fermentable foods that often cause bloating and other symptoms in patients with irritable bowel syndrome. In the study, a low FODMAP diet combined with L-glutamine reduced symptom scores by 45% or more in 88% of patients as compared to 60% of patients on the low FODMAP diet alone.

Like probiotics, soluble fiber, and peppermint oil, L-glutamine may be another option to improve gastrointestinal function in patients struggling with symptoms of irritable bowel syndrome.

L-Glutamine and Immune Function

Beyond intestinal health, L-glutamine is also critical for immune function. When the immune system is strongly activated, glutamine stores can be used up. Intense physical activity can also deplete L-glutamine stores. In these situations, supplying additional glutamine can help to maintain proper immune function, yielding potential benefits.

While not all of the studies are consistent, studies on patients undergoing peritoneal dialysis, heavy load training, high altitude training, and intensive judo training have shown that supplementing L-glutamine or alanyl-glutamine can maintain or support immune function. Peritoneal dialysis is a medical technique to filter the blood in patients struggling with kidney failure. A tube is placed in the abdomen through which dialysis, or blood filtration, takes place. A side effect of peritoneal dialysis is an infection at the site of the abdominal tube. Preliminary research suggests that infections might be reduced with alanyl-glutamine supplementation.

Burn patients also commonly struggle with infections that can be life-threatening. A study out of Africa found a reduction of infections by one-third with L-glutamine in severe burn patients. A separate study in China found that L-glutamine also corrected immune dysfunction in severe burn patients. A meta-analysis even identified potential benefits of L-glutamine for burn patients, but more research is needed to confirm the findings.

Takeaway

L-glutamine appears to have beneficial effects for irritable bowel syndrome, leaky gut, and certain situations predisposing individuals to reduced immune function. Supplementation typically consists of fairly large doses, anywhere from a few grams up to 30 grams taken throughout the day. In the literature, side effects are typically minimal as L-glutamine is well tolerated, even at these large doses.

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