summary

Abstracts

Summary

Ornithine is a non-essential amino acid derived from the breakdown of arginine in the liver. It helps build muscle and reduce body fat, especially when combined with the amino acids arginine and carnitine. Ornithine is also needed for the formation of citrulline, proline, and glutamic acid, three amino acids that help supply energy to every cell in the body. Most of the beneficial effects of ornithine are carried out as a salt called ornithine alpha-ketoglutarate. Laboratory studies have shown that ornithine increases both insulin and growth hormone levels. Ornithine also plays a role in the healing of wounds following trauma and burn. Ornithine is generally thought to be twice as effective at stimulating growth hormone production as arginine. Though the body can manufacture its own ornithine, good dietary sources are meat, fish, dairy, and eggs.  (For more detailed information, please visit ISM’s searchable database: Nutraceutical Search.)

Ornithine alpha-ketoglutarate (OKG) is a salt formed of two molecules of ornithine and one molecule of alpha-ketoglutarate. OKG has been successfully used by the enteral and parenteral route in burn, traumatized, and surgical patients and in chronically malnourished subjects. According to the metabolic situation, OKG treatment decreases muscle protein catabolism and/or increases synthesis. In addition, OKG promotes wound healing. The mechanism of action of OKG is not fully understood, but the secretion of anabolic hormones (insulin, human growth hormone) and the synthesis of metabolites (glutamine, polyamines, arginine, ketoacids) may be involved.

o      Cynober L (1991). Ornithine alpha-ketoglutarate in nutritional support. Nutrition, 7(5), 313-22.

Theoretically, alpha-ketoglutarate is a precursor of glutamine, a fact that may be of importance given the key regulatory properties of this amino acid. Although the literature suggests that glutamine synthesis accounts only for a marginal part of the disposal of exogenously supplied alpha-ketoglutarate, administered alpha-ketoglutarate has a potent 'sparing' effect on endogenous glutamine pools. When alpha-ketoglutarate is supplied as an ornithine salt, a synergistic effect of the two parts of the molecule increases the synthesis of glutamine or the 'sparing' of endogenous glutamine pools. In addition, alpha-ketoglutarate in combination with ornithine dramatically increases the synthesis of arginine, proline and polyamines, which also play key roles in metabolic adaptation to trauma. The recent literature suggests that the administration of alpha-ketoglutarate in combination with ornithine improves gut morphology and functions, counteracts trauma-induced dysimmunity and exerts anabolic/anticatabolic actions on protein metabolism.

 o      Cynober, L (1999). The use of alpha-ketoglutarate salts in clinical nutrition and metabolic care. Curr Opin Clin Nutr Metab Care, 2(1), 33-7.

To investigate appropriate mode and daily dose of enteral ornithine alpha-ketoglutarate (OKG) administration, 54 burn patients (total burn surface area: 20-50%) were included in a randomized controlled trial and assigned to receive either a supplement of OKG (10, 20 or 30 g/d) as bolus or continuous infusion, or a continuous infusion of an isonitrogenous amount of a soy protein mixture (Protil-1: 10, 20 or 30 g/d) in addition to their enteral diet……….. This study further supports OKG supplementation in burn patients.

 o      De Bandt, JP, Coudray-Lucas, C, Lioret, N, Lim, SK, Saizy, R, Giboudeau, J & Cynober, L (1998). A randomized controlled trial of the influence of the mode of enteral ornithine alpha-ketoglutarate administration in burn patients. J Nutr. 128(3), 563-9. 

OBJECTIVE: To compare the effectiveness on wound healing time in severe burn patients of ornithine alpha-ketoglutarate supplementation of enteral feeding vs. an isonitrogenous control. Previous clinical and experimental studies suggest a beneficial effect of enterally administered ornithine alpha-ketoglutarate supplementation on protein metabolism in burn patients, but few data deal with clinical outcome……….. CONCLUSIONS: Ornithine alpha-ketoglutarate supplementation of enteral feeding significantly shortens wound healing time in severe burn patients. In addition, ornithine alpha-ketoglutarate administration was safe and well tolerated and decreased protein hypercatabolism in the less severe burn patients.

 o      Coudray-Lucas, C, Le Bever, H, Cynober, L, De Bandt, JP & Carsin, H. (2000). Ornithine alpha-ketoglutarate improves wound healing in severe burn patients: a prospective randomized double-blind trial versus isonitrogenous controls. Crit Care Med. 28(6), 1772-6.

Relative deficiencies of ornithine or arginine occur in the presence of excessive ammonia, excessive lysine, growth, pregnancy, trauma, or protein deficiency and malnutrition. Ammonia excess may occur in the presence of a normal liver when amino acid mixtures lacking ornithine, arginine, or citrulline are infused………In these states, ornithine is often rate-limiting for urea cycle function. Ornithine is also rate-limiting when ammonia excess occurs in the presence of hepatic failure. In three of the inherited urea cycle disorders, ornithine insufficiency and ammonia excess also occur……….. Protein deficiency and malnutrition increase the vulnerability of the animal or child to ammonia toxicity. This is presumably due to insufficient ornithine for normal urea cycle responsiveness.

o      Zieve, L (1986). Conditional deficiencies of ornithine or arginine. J Am Coll Nutr. 5(2) 167-76.

Background. Supplemental arginine has been shown to enhance wound healing, in particular collagen synthesis. Ornithine is the main metabolite of arginine in the urea cycle and shares many of the biopharmacologic effects of arginine. The present study examines the effect of ornithine supplementation on wound healing and attempts to describe its possible mechanism……….. Conclusion. The results from this study demonstrate that ornithine supplementation enhances wound healing.

o      Shi, HP, Fishel, RS, Efron, DT, Williams, JZ, Fishel, MH & Barbul, A (2002). Effect of Supplemental Ornithine on Wound Healing. J Surg Res. 106(2), 299-302.

Arginine and ornithine are precursors of nitric oxide and polyamines, respectively. These metabolites intimately participate in permeability and adaptive responses of the gut. The liver possesses high arginase activity as an intrinsic part of urea synthesis and would consume most of the portal supply of dietary arginine……… Dietary ornithine supplementation, in the form of ornithine alpha-ketoglutarate (OKG) can be considered as an arginine precursor. Several supplement studies have shown both amino acids to promote growth hormone and insulin secretion with anabolic effects in postoperative patients. Their intermediary metabolites (for example, glutamine, proline) may also be of benefit in trauma metabolism……….. These considerations suggest that the role of enteral diet supplementation with arginine or OKG should be urgently examined for any benefits it may have on mucosal barrier function.

o      Cynober L (1994). Can arginine and ornithine support gut functions? Gut, 35(1 Suppl), S42–S45.

BACKGROUND: Ornithine alpha-ketoglutarate (OKG) has proved to be efficient in restoring glutamine (Gln) pools which are strongly depleted in hypercatabolic patients. Since its two components, alpha-ketoglutarate (alphaKG) and ornithine (Orn), give rise to glutamate (Glu), they are both considered as Gln precursors. The aim of this study was to assess the relative contributions of Orn and alphaKG to Gln generation in a rat model of burn injury……….. CONCLUSION: OKG was more efficient than Orn or alphaKG alone in restoring Gln pools in plasma and muscle, which is evidence of metabolic interaction between the two components of this molecule.