Impact of Glutamine-Rich Foods on Immune Function - Medicinal Properties in Whole Foods - Statistical Data Included

Townsend Letter for Doctors and Patients, April, 2002 by Gina L. Nick

"Functional foods," "nutraceuticals," "designer foods" and "medicinal foods" are terms that describe foods, and key ingredients isolated from foods, that have non-nutritive or tertiary functional properties. Researchers, healthcare practitioners, laypersons, and the popular media use these words interchangeably. The purpose of this article is to detail valid scientific information available on whole food cardioprotectants (whole grains, fruits, vegetables and phytoestrogens) that may augment the cardiovascular risks associated with hormone replacement therapy (HRT) in women.

Messenger molecules, growth factors and other effectors of immune cell function are made up of soluble elements that impact immune response. Examples of such factors include glutamine (an essential substrate for cell division and energy production in lymphocytes, enterocytes and macrophages), antibodies and immunoglobulins (produced by mature B lymphocytes) and cytokines (growth factors produced by leukocytes and other cells). The actions of glutamine are particularly important when one wants to utilize whole foods to improve or stabilize the immune response.

Glutamine is found most abundantly in high protein foods, such as meat, fish, legumes, and dairy. Two particularly high vegetable sources are raw (uncooked) cabbage and beets. (1-5) It is known that cooking can destroy glutamine, particularly in vegetables. In addition, cabbage in particular appears to contain "unknown" effective components that, when ingested and absorbed from the gastrointestinal tract, stimulate the production of tumor necrosis factor [alpha] (TNF[alpha]) and interleukin-1 (IL-1), important players in antitumorial, antiviral, immunoregulatory, and inflammatory responses. (6) Further, cabbage contains glucosinolates and their breakdown products that show clear benefits in optimizing immune function. (7)

Glutamine

Glutamine is the most abundant amino acid in the bloodstream (30-35% of amino acid nitrogen in plasma) and fills a number of biochemical needs in the body. (8) It is a conditionally-essential amino acid, in that the human body produces it endogenously. Deficiencies are prevalent however, primarily as a result of cancer, burns, trauma, chronic protein catabolism and excessive exercise. (9,10) While glutamine is largely formed and stored in skeletal muscle and in the lungs, (11) it is the main metabolic fuel for enterocytes of the small intestine, lymphocytes, macrophages, and fibroblasts and plays a major role in the first line of immune defense in the intestine as well as in the body as a whole.

Research suggests that glutamine is essential to the health and maintenance of the intestinal tract. (12,13) In fact, the intestine, and particularly the small intestine, is the greatest user of glutamine in the body. The intestinal enterocytes absorb glutamine from the lumen of the gut and the bloodstream. The intestinal cell mitochondria then convert glutamine to glutamate, and then to alpha-ketoglutarate, which is used in the Krebs cycle for ATP production (Figure 1).

Studies have shown that the level of stored glutamine drops significantly in humans following surgery, trauma, or burns, as well as during sepsis. (14-16) Its deficiency has been implicated in immune dysfunction because it serves as a main precursor of nucleotide synthesis and also as an energy source for rapidly dividing cells, such as immune cells following an immune threat. (17-19)

Mechanisms of Action of Glutamine

Lymphocytes use a large amount of glutamine, even in the resting state. (20) However, they show no signs of glutamine synthetase activity in vitro, suggesting that lymphocytes are dependent upon pre-formed glutamine from other sources. Consequently, as lymphocytes are activated, their consumption of glutamine increases. Lymphocytes respond to glutamine by proliferating and producing more lymphocyte-derived cytokines. (21-23) Glutamine is also required for the activation of T cells, possibly because it stimulates entry into the cell cycle and expression of the "late" activation markers, CD71 and CD45RO. (24) It is also necessary for interleukin-2 production by spleen lymphocytes. (25)

Prevention of Microbial Translocation

Glutamine's positive effect on the GI tract appears to be due to its use as a food source by both intestinal immune cells (lymphocyte-rich Peyer's patches) and mucosal cells. Intestinal epithelial cells contain very low levels of glutamine synthetase and hence are largely dependent on pre-formed glutamine, either from the diet or from the blood. If glutamine is lacking in the diet, or if a person is being fed parenterally due to illness, intestinal cells will take glutamine from the bloodstream at the expense of muscle tissue, thus depleting the body's stores. (26)

This depletion of glutamine from muscle is a major cause of cachexia observed in critically ill patients. (27) When levels of glutamine drop, intestinal epithelial cells and lymphocytes begin to lose function, compromising the integrity of the epithelium and leaving the intestine vulnerable to microbial translocation (passage of bacteria or toxins into the bloodstream via the intestinal wall) and subsequent risk of sepsis. (28-33) Several factors can disrupt intestinal permeability leading to increased microbial translocation, including: