Glutamine, Essential Nutrient in Oncology

Immunonutrition refers to the addition of specific nutrients to oral, enteral or parenteral nutrition regimens, in concentrations greater than normal, to achieve a pharmacological effect that regulates immune function. It modulates the immune response by administering certain nutrients or pharmaconutrients called organ-specific diets.

Immunonutrition goes beyond improving the nutritional status of the patient, so it has 3 fundamental pillars:

1.- In cell defense.
2.- As a barrier function of the intestinal mucosa.
3.- In both local and systemic inflammation.

“When talking about immunonutrition it is important to take into account the bases that dictate the function of the immune system on the one hand, and on the other the nutritional situation of the patient with Cancer. The immune system protects the organism from attack by pathogens, it is our “organ” or defense system. In addition, the immune system also acts to ensure tolerance of its own, of the intake of food and other environmental components, as well as of the bacteria inherent in the organism that make up the microbiota or intestinal flora. However, if there is a failure in the tolerance pathways, an inflammatory process may occur ”; says clinical nutritionist, Sandra Cristina Rangel.

 How to Direct the Cancer Patient Regarding Nutrition Therapy?

Clinical studies demonstrate evidence of initiating nutritional therapy with immunomodulatory nutrients (also known as pharmaconutrients), as they modulate the immune response. One of the most studied immunomodulatory nutrients is glutamine.

Glutamine is the most abundant amino acid in the body . It is a conditionally essential amino acid, called conditionally essential because in special circumstances: critical or pathological disease as in Cancer, production is insufficient and they become essential; The demands of this amino acid increase so its supplementation is of importance to maintain the integrity and functionality of the intestine to repair the intestinal mucosa, restore the intestinal microbiota and regenerate intestinal health.

Glutamine is the biological fuel for intestinal cells (called enterocytes ) and immune system; In the small intestine, glutamine is particularly important as it is the preferred source for these sterocytes and the large mass of immune cells of the lymphoid tissue associated with the intestine by its acronym in English (GALT). Glutamine provides an important part of intestinal energy, considered the best cellular fuel including enterocytes, reticulocytes, lymphoblasts and fibroblasts.

In clinical situations such as trauma, sepsis and Cancer, their tissue concentrations decrease, which brings with it fatal consequences for the organism, such as the imbalance of protein synthesis and the breakdown of the gastrointestinal tract’s barrier function.

“Intestinal Cells, Also Called Enterocytes”

Physiologically, metabolic needs are predominantly covered by endogenous synthesis and subsequent release of skeletal muscle and, to a lesser effect, from the lung. In healthy adults, nutritional intake plays a minor role.

Recently, it has been shown in various lines of research that cells of tumor and non-tumor origin, cell growth is a function of glutamine availability. By mobilizing and increasing circulating glutamine, tumor cells induce a net flow of glutamine from the host tumor.

In patients with progressive cancer, glutamine released from skeletal muscle into the bloodstream increases even further, resulting in a considerable decrease in intramuscular glutamine concentrations. The resulting deprivation of glutamine to the host leads to adverse effects on the immune status of the cancer patient, integrity of the gastrointestinal mucosa, and the host protein and energy metabolism.

It has been suggested that the interruption of the interorganic flow – glutamine is due to the progressive growth of the tumor; which can contribute essentially to the appearance of metabolic alterations due to the lack of glutamine available in the cancer patient; such as cachexia which is a complex syndrome characterized by weight loss, anorexia and asthenia, with metabolic alterations; They include insulin resistance, hyperlipidemia, loss of adipose tissue, loss of muscle mass and reduces the function of the intestinal barrier.

The most important factors to consider are the side effects of chemotherapy and radiotherapy, anorexia, mucositis, dysphagia, nausea, vomiting, diarrhea, enteritis, ulcerations, necrosis, xerostomia and insufficiency hepatic

As for the alteration of protein metabolism, there is an increase in protein turnover, due to:

  • Increased Hepatic Protein Synthesis
  • Increased Muscle Protein Degradation
  • Alteration of Protein Synthesis

Glutamine Metabolism in Health and Cancer

Glutamine consumption occurs largely in the intestine and kidney. The organs of the gastrointestinal tract drained by the portal vein, especially the small intestine, are large consumers of Plasma Glutamine. Enterocytes oxidize more than half of the glutamine carbon to CO2; which represents for one third of the fasting of these fasting cells.

The kidney consumes net amounts of glutamine to maintain acid-base balance. During acidosis, the kidneys substantially increase their uptake of glutamine for ammonia production; It is excreted together with organic acids and maintain the physiological pH. Glutamine is also an important metabolic substrate in lymphocytes and macrophages.

In summary, Glutamine for its role in the protection and restoration of the gastrointestinal tract; It helps better interaction between nutrients and the immune system in patients receiving therapies such as chemotherapy and / or radiotherapy.

Although still, there is no consensus on the routine administration of Glutamine in Cancer; Clinical evidence has shown by some authors that the indication of glutamine supplementation may stop tumor growth due to its immunomodulatory action; as well as decrease in patients with advanced malignancies, prophylaxis in mucositis, diarrhea and control weight loss.

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