Glutamine Peptides
vs L-glutamine
DESCRIPTION
Glutamine peptides refer to certain dipeptides used in total parenteral
nutrition (TPN) as delivery forms of L-glutamine. The term also refers to
peptides containing L-glutamine, which are found in some nutritional
supplements, particularly those marketed as sports and fitness products.
L-glutamine depletion is a typical feature of such metabolic stress conditions as trauma (including surgical trauma), infection, sepsis, cancer and severe burns. The metabolic response to these conditions is characterized by catabolism and negative nitrogen balance. Under these conditions, L-glutamine, which is normally manufactured by the body (mainly in skeletal muscles) in sufficient quantities to satisfy physiological demands, is required exogenously. Under these conditions, L-glutamine becomes an essential amino acid and must be supplied to the body in order to prevent breakdown of muscle tissue, immune dysfunction and compromise of the gut mucosal barrier function with consequent bacterial translocation into the body. L-glutamine is arguably the most needed amino acid and, indeed, one of the most needed nutrients under these circumstances.
Until recently, L-glutamine was lacking from TPN. The reason for this is because L-glutamine is not very soluble in water^one gram dissolves in 20.8 ml of water at 30 degrees Celsius^and L-glutamine is unstable in solution. The problem has been solved by the synthesis of glutamine-containing dipeptides, which are very soluble in water and stable in solution.
Two synthetic glutamine-containing dipeptides that may be used in TPN are L-alanyl-L-glutamine (Ala-Gln) and glycyl-L-glutamine (Gly-Gln). The molecular weight of Ala-Gln is 217.24 daltons, and L-glutamine comprises 67% of the dipeptide. L-glutamine comprises 72% of Gly-Gln, and its molecular weight is 203.22 daltons.
ACTIONS AND PHARMACOLOGY
ACTIONS
Glutamine peptides may have immunomodulatory, anticatabolic/anabolic, gut
mucosal barrier-protective and antioxidant actions.
MECHANISM OF ACTION
The glutamine dipeptides, Ala-Gln and Gly-Gln, have demonstrated
immunomodulatory, anticatabolic/anabolic, gastrointestinal mucosal
protective and antioxidant activities when used in TPN. These activities
have not yet been demonstrated with glutamine peptides marketed as
nutritional supplements for fitness purposes. The mechanism of the
immunomodulatory action of the glutamine dipeptides is unclear. The
mechanism may in part be due to the ability of L-glutamine to ameliorate the
negative effects of TPN on the immune system. Also, L-glutamine is the
preferred respiratory fuel for lymphocytes and appears to be required to
support the proliferation of mitogen-stimulated lymphocytes, as well as the
production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). It also
appears to be required for the maintenance of lymphokine-activated killer
cells (LAK). It can also enhance phagocytosis by neutrophils and monocytes.
The anticatabolic/anabolic action of the glutamine dipeptides can be explained by their effect in sparing skeletal muscle L-glutamine stores. Most of the L-glutamine in the body is synthesized in skeletal muscle, where it is also stored. Under conditions of metabolic stress, skeletal muscle can be depleted of its L-glutamine, which is used for metabolic activities of other tissue/cells, such as enterocytes and lymphocytes.
The gastrointestinal mucosal-protective effect of the glutamine
dipeptides can be explained in a few ways. L-glutamine is the preferred
respiratory fuel for enterocytes and colonocytes. Maintaining the
bioenergetics of these cells is fundamental to maintaining the integrity of
the intestine. In addition, L-glutamine helps maintain secretory IgA, which
functions primarily by preventing the attachment of bacteria to mucosal
cells. L-glutamine may inhibit translocation of Gram-negative bacteria from
the intestine into the body.
Metabolic stress goes hand in hand with oxidative stress. L-glutamine can
help in ameliorating oxidative stress by serving as precursor to
glutathione.
PHARMACOKINETICS
Glutamine dipeptides in TPN are transported via the circulation to the
various tissues of the body, where they are taken up by cells and
metabolized. Ala-Gln is first metabolized to L-alanine and L-glutamine,
while Gly-Gln is metabolized to glycine and L-glutamine. L-glutamine
participates in various metabolic activities, including the production of
L-glutamate and other amino acids, glutathione, energy, proteins, pyrimidine
and purine nucleotides and amino sugars. L-glutamine is eliminated by
glomerular filtration and is almost completely reabsorbed by the renal
tubules.
Most of the glutamine dipeptides administered orally or enterally are
absorbed intact from the lumen of the small intestine into the enterocytes.
A portion of the glutamine dipeptides gets metabolized within the
enterocytes. That which is not metabolized enters the portal circulation
from whence it is transported to the liver. Again, some metabolism takes
place in the liver, and that portion not metabolized enters the systemic
circulation and is distributed to various tissues of the body.
INDICATIONS AND USAGE
Like glutamine itself (see Glutamine), the dipeptide forms added to TPN are
credited with helping in the recovery of trauma, surgical and other
critically ill patients. There is as yet no credible evidence that oral use
of glutamine peptide supplements has anabolic or ergogenic effects in those
who are not metabolically compromised.
RESEARCH SUMMARY
Studies have shown that glutamine and glutamine dipeptides exert similar
metabolic effects. The dipeptides themselves are now being used in clinical
nutrition.
In one recent, double-blind, randomized, controlled study, duration of
hospital stay was significantly reduced in patients who had undergone major
abdominal surgery and who had received glutamine dipeptides via TPN over a
five-day period. Mean cumulative nitrogen balance was significantly better
in these patients, as was immune function, as measured by lymphocyte counts
and generation of cysteinyl leukotrienes by polymorphonuclear neutrophils, a
measure of neutrophil function.
CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS
CONTRAINDICATIONS
Glutamine peptides are contraindicated in those hypersensitive to any
component of a glutamine peptide-containing product.
PRECAUTIONS
The use of glutamine dipeptides in TPN must be done under medical
supervision. Those with renal and liver failure should exercise caution in
the use of glutamine peptide supplements.
Pregnant women and nursing mothers should avoid the use of oral glutamine
peptide supplements unless prescribed by their physicians.
ADVERSE REACTIONS
There are rare reports of constipation and bloating with high dose glutamine
peptides in TPN.
OVERDOSAGE
No reports of overdosage.
DOSAGE AND ADMINISTRATION
The use of glutamine dipeptides in TPN is relatively recent. The two
synthetic dipeptides used are L-alanyl -L-glutamine and glycyl-L-glutamine.
Doses suggested (given as L-glutamine) are 12 grams daily for surgical
trauma and about 25 grams daily for severe trauma and infections.
Those who use oral glutamine peptide supplements for fitness or sports
purposes use 1.5 to 4.5 grams (as L-glutamine) daily.
OUR OPINION OF L-GLUTAMINE
As a dietary or performance enhancing recovery supplement, through research
and testing we at physical-sciences have found free form l-glutamine to be a
completely worthless supplement. L-glutamine at the point of digestion was
destroyed over 85% by the human digestive system.
LITERATURE
Decker-Baumann C, Buhl K, Frohmuller S, et al. Reduction of
chemotherapy-induced side-effects by parenteral glutamine supplementation in
patients with metastatic colorectal cancer. Eur J Cancer. 1999; 35:202-207.
Furst P, Pogan K, Stehle P. Glutamine dipeptides in clinical nutrition. Nutrition. 1997; 13:731-737.
Khan J, Iiboshi Y, Cui L, et al. Alanyl-glutamine-supplemented parenteral nutrition increases luminal mucus gel and decreases permeability in the rat small intestine. J Parenter Enteral Nutr. 1999; 23:24-31.
Li YS, L. JS, Jiang JW, et al. Glycyl-glutamine-enriched long-term total parenteral nutrition attenuates bacterial translocation following small bowel transplantation in the pig. J Surg Res. 1999; 82:106-111.
Minami H, Morse EL, Adibi SA. Characteristics and mechanism of glutamine-dipeptide absorption in human intestine. Gastroenterology. 1992; 103:3-11.
Morlion BJ, Stehle P, Wachtler P, et al. Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: a randomized, double-blind, controlled-study. Ann Surg. 1998; 227:302-308.
Schroder J, Kahlke V, Fandrich F, et al. Glutamine dipeptide-supplemented parenteral nutrition reverses gut mucosal structure and interleukin-6 release of rat intestinal mononuclear cells after hemorrhagic shock. Shock. 1998; 10:26-31.