Ornithine Alpha-Ketoglutarate for Burn Victums, Muscle Wasting, Etc.

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Ornithine Alpha-Ketoglutarate

DESCRIPTION

Ornithine alpha-ketoglutarate, abbreviated OKG, also known as ornithine

2-oxoglutarate or ornithine oxoglutarate (OGO), is a salt formed of two

molecules of the non-protein amino acid, L-ornithine, and one molecule of the

Krebs cycle dicarboxylic acid, alpha-ketoglutarate. OKG has been used both

enterally and parenterally in burn, trauma, surgical and chronically

malnourished patients. It appears to decrease protein catabolism and/or increase

protein synthesis under these conditions. OKG is a popular nutritional

supplement for athletes, among others.

ACTIONS AND PHARMACOLOGYACTIONS

OKG, under certain conditions, may have immunomodulatory and anticatabolic

and/or anabolic actions. OKG is a delivery form of L-glutamine and L-arginine

precursors.

MECHANISM OF ACTION

The actions of OKG can be attributed to the metabolites that the OKG components,

L-ornithine and alpha-ketoglutarate, give rise to. These metabolites are

L-arginine, L-glutamine, L-proline and polyamines. The metabolism of L-glutamine

and L-arginine is altered in trauma, and this alteration is linked to immune

dysfunction.

 

One of the major biochemical events that occurs following a burn injury is a

fall in intramuscular L-glutamine. This amino acid is released from muscle

tissue to meet the increased needs of other cells, in particular immune cells

and intestinal cells. L-glutamine is now known to be essential for sustaining

the proliferation and activation of immune cells. In the intestine it is

essential for maintaining the integrity of the mucosal barrier and its metabolic

and immune function. Immune and gastrointestinal dysfunctions occur when de novo

L-glutamine synthesis is insufficient to maintain normal function of immune

cells and enterocytes. Under these conditions, for example a burn injury, the

normally non-essential (meaning the body can make it) L-glutamine becomes a

conditionally essential amino acid (meaning the body can't make enough of it).

OKG is a delivery form of L-glutamine.

 

L-arginine is also essential for immune cells. It is thought that the role of

L-arginine in immunity is mediated by its metabolite nitric oxide. Burn injury

and some other traumas affect the status of both L-glutamine and L-arginine in

the various tissues of the body, especially muscle, the immune system and the

gastrointestinal tract. As in the case of L-glutamine, de novo synthesis of

L-arginine during these conditions is probably not sufficient for normal immune

and gastrointestinal function, nor for normal protein synthesis. OKG, in

addition to being a delivery form of L-glutamine, is also a delivery form of

L-arginine or more precisely L-ornithine, which is converted to L-arginine.

 

It is unclear if OKG has immunomodulatory or anticatabolic/anabolic actions

under normal conditions.

 

See L-Glutamine and L-Arginine.

PHARMACOKINETICS

Following ingestion, OKG is absorbed from the small intestine from whence it is

transported to the liver. In the liver, OKG enters various metabolic pathways.

L-ornithine is a precursor in the synthesis of L-arginine and polyamines, among

others. Alpha-ketoglutarate is metabolized to L-glutamine, among other

molecules. OKG not metabolized by the liver is transported via the systemic

circulation and distributed to various tissues of the body, including the brain,

where it undergoes metabolic reactions similar to those above. Under conditions

of trauma or burn injury, OKG may be metabolized in immune cells, enterocytes

and muscle tissue to produce L-arginine and L-glutamine.

INDICATIONS AND USAGE

OKG has demonstrated significant usefulness in the nutritional support of burn

and other trauma patients, as well as in chronically malnourished subjects and

post-surgery in the elderly. It has been shown to speed wound healing. It has

exhibited some immunomodulating effects. Claims that it enhances athletic

performance have not been confirmed.

RESEARCH SUMMARY

OKG has shown significant effects related to nutritional support in burn,

trauma, surgical, elderly and chronically malnourished subjects. These effects

have been achieved with both enteral and parenteral administration. OKG has been

shown, in varying conditions, to decrease muscle protein catabolism and/or

increase muscle protein synthesis. It has also been shown to enhance wound

healing. Its ability to increase synthesis of L-glutamine and L-arginine may

account for these positive effects. In a recent double-blind, placebo-controlled

study, 60 severely burned subjects were randomized to receive 20 grams of OKG

daily or placebo for 21 days beginning mean four days post-injury. Significant

improvement was achieved in the OKG-treated group, compared with controls, as

measured by both biological and clinical end points. Previous studies of

OKG-treated burn patients have reported shorter hospitalizations and fewer

fatalities.

 

No conclusions can yet be drawn from scant, preliminary evidence that OKG may

exert some positive effects on immunity. And there is no credible research to

support claims that OKG can build muscle in healthy individuals or that it can

enhance exercise/athletic performance.

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONSCONTRAINDICATIONS

OKG is contraindicated in those with deficiency of

ornithine-delta-aminotransferase (OAT). This is a genetic disease resulting in

gyrate atrophy of the choroid and retina and progressive blinding chorioretinal

degeneration. It is rare.

PRECAUTIONS

Pregnant women and nursing mothers should avoid supplemental OKG. OKG

supplementation may potentially cause hypoglycemia in starved individuals. Those

with eating disorders or those who are on very-low-calorie diets should exercise

caution in using OKG.

ADVERSE REACTIONS

None reported for those using supplemental OKG.

DOSAGE AND ADMINISTRATION

There are no typical doses for OKG supplementation. Some athletes use about 2.5

grams before and after exercise, as well as before breakfast and at bedtime.

 

Doses of 20 to 30 grams daily, given enterally, have been used in burn and

trauma patients.

HOW SUPPLIED

Powder — 3.5 mg/teaspoonful

LITERATURE

Czernichow B, Nsi-Emvo E, Galluser M, et al. Enteral supplementation with

ornithine alpha ketoglutarate improves the early adaptive response to resection.

Gut. 1997; 40:67-72.

 

De Bandt JP, Coudray-Lucas C, Lioret N, et al. A randomized controlled trial of

the influence of the mode of enteral ornithine alpha-ketoglutarate

administration in burn patients. J Nutr. 1998; 128:563-569.

 

Dumas F, De Bandt JP, Colomb V, et al. Enteral ornithine alpha-ketoglutarate

enhances intestinal adaptation to massive resection in rats. Metabolism. 1998;

47:1366-1371.

 

Donati L, Ziegler F, Pongelli G, Signorini MS. Nutritional and clinical efficacy

of ornithine alpha-ketoglutarate in severe burn patients. Clin Nutr. 1999;

18:307-311.

 

Duranton B, Schleiffer R, Gosse F, Raul F. Preventive administration of

ornithine alpha-ketoglutarate improves intestinal mucosal repair after transient

ischemia in rats. Crit Care Med. 1998; 26:120-125.

 

Jeevanandam M, Holaday NJ, Petersen SR. Ornithine-alpha-ketoglutarate(OKG)

supplementation is more effective than its component salts in traumatized rats.

J Nutr. 1996; 126:2141-2150.

 

Jeevanandam M, Petersen SR. Substrate fuel kinetics in enterally fed trauma

patients supplemented with ornithine alpha-ketoglutarate. Clin Nutr. 1999; 18;

209-217.

 

Le Boucher J, Eurengbiol, Farges MC, et al. Modulation of immune response with

ornithine A-ketoglutarate in burn injury: an arginine or glutamine dependency?

Nutrition. 1999; 15; 773-777.

 

Le Bricon T, Cynober L, Baracos VE. Ornithine alpha-ketoglutarate limits muscle

protein breakdown without stimulating tumor growth in rats bearing Yoshida

ascites hepatoma. Metabolism. 1994; 43; 899-905.

 

Le Bricon T, Cynober L. Field CJ, Baracos VE. Supplemental nutrition with

ornithine alpha-ketoglutarate in rats with cancer-associated cachexia: surgical

treatment of the tumor improves efficacy of nutritional support. Nutr. J 1995;

125:2999-3010. *rp Robinson LE, Bussiere FI, Le Boucher J, et al. Amino acid

nutrition and immune function in tumour-bearing rats: a comparison of

glutamine-, arginine- and ornithine 2-oxoglutarate-supplemented diets. Clin Sci

(Colch). 1999; 97:657-669.

 

Roch-Arveiller M, Fontagne J, Coudray-Lucas C, et al. Ornithine

alpha-ketoglutarate counteracts the decrease of liver cytochrome p-450 content

in burned rats. Nutrition.1999; 15:379-383.

 

Roch-Arveiller M, Tissat M, Coudray-Lucas C, et al. Immunomodulatory effects of

ornithine alpha-ketoglutarate in rats with burn injuries. Arch Surg. 1996;

131:718-723.

 

Varanasi RV, Saltzman JR. Ornithine oxoglutarate therapy improves nutrition

status. Nutr Rev. 1996; 53:96-97.

 

 

 

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