The bidirectional communication between the gut and the brain, known as the gut-brain axis, plays a vital role in the human body. The vagus nerve, the tenth cranial nerve, facilitates this communication via the enteric nervous system. Optimal brain function may promote optimal gut function, and vice versa. In this interconnected relationship, L-glutamine may play a unique role in supporting this communication. 

During periods of physical stress (e.g., surgery, illness, high-intensity exercise) or psychological stress, maintaining proper L-glutamine status is pivotal. Stress, whether acute or chronic, can disrupt gut health, mental health, and L-glutamine status in the body. L-glutamine, the most abundant amino acid in the body, is conditionally essential. Although the body can typically synthesize sufficient amounts of L-glutamine for overall health, stress increases the demand for L-glutamine, requiring exogenous sources from food or supplementation.

L-glutamine can be obtained from various foods in the modern diet, including beef, pork, milk, cheese, cabbage, parsley, and spinach. However, supplements may be warranted for certain individuals with unhealthy stress responses if these foods are not part of their regular diet. For instance, consuming 15 ounces of beef provides only 5 g of L-glutamine. 

L-glutamine has demonstrated multiple clinical benefits for gut health, such as promoting enterocyte function and proliferation, maintaining a healthy gut microbial environment, supporting gut barrier integrity and function, and regulating inflammatory and immune responses. When L-glutamine stores are depleted due to stress, “the intestinal lining is left even more vulnerable to cumulative damage.” When this occurs, everyday environmental toxins, such as harsh chemicals from foods, water, and personal and household products, may place an even greater burden on the gut and its immune response.

By supporting intestinal health and a balanced gut microbiome, L-glutamine may help promote mental health by way of the gut-brain axis. While additional research is needed, a healthy gut microbial environment and proper intestinal function may promote healthy brain development and neurotransmitter production. Serotonin, dopamine, norepinephrine, gamma-aminobutyric acid (GABA), acetylcholine, histamine, and glutamate are among the neurotransmitters that may be positively affected by healthy gut barrier function and microbial balance. 

Gut health may also promote proper hormonal balance through the hypothalamic-pituitary-adrenal axis (HPA axis), according to a preliminary study in healthy infants. Stress or perceived threats activate the HPA axis to secrete various hormones, including cortisol. This system may be dysregulated in major psychiatric disorders or states of chronic stress. Therefore, focusing on gut health may be clinically beneficial in supporting a healthy HPA axis. 

Lastly, L-glutamine further supports mental health by serving as a precursor to the neurotransmitters GABA and glutamate. Poor gut health can disrupt neurotransmitter balance, which can affect overall mood and mental health.

The amino acid L-glutamine has the potential to simultaneously support gut health and mental health. The proper status of this conditionally essential amino acid may be particularly important for individuals with unhealthy stress responses, as acute or chronic stress can negatively impact both gut and mental health and deplete L-glutamine stores in the body.

By Danielle Moyer, MS, CNS, LDN