Also known as OKG, this compound is formed from two molecules of the amino acid ornithine and one a-KG. OKG has been shown in a variety of studies to have an anabolid anticatabolic effect. OKG has been used successfully via enteral or parenteral administration in conditions such as burn, postsurgery, malnutrition, and wound healing. The mechanism by which OKG exerts these effects is not known; however, the secretion of hormones such as insulin and growth hormone and the conversion to other metabolites (e.g., glutamine, arginine, etc.) might play a role.



Animal Studies

Vaubourdolle et al. used an animal burn model to study the effects of OKG administration during a hypercatabolic state. Rats were studied after having their dorsum in water at 90°C for 10 seconds (inducing a burn injury) and then starved for 24 hours. The supplementation of OKG (5 g/kg/day) for 2 days decreased the level of muscle mass loss and increased intramuscular glutamine concentration. An isonitrogenous amount of glycine had no effect. Similar work by Le Boucher et al found that OKG inhibits myofibrillar degradation in burn-injured rats while glycine had no such effect. In an interesting study using malnourished animals, male rats were starved for 3 days, then refed for 7 days with an oral diet (192 kcal kg/day; 2.25 g/kg/day of nitrogen) supplemented with either OKG, glutamine, or casein Starvation caused a drop in most tissue-amino acids except skeletal muscle leucine (+43%) and liver glutamate (+ 11 %). The primary effect of OKG was to normalize the amino acid concentrations in the liver and small bowel while glutamine normalized glutamine and leucine concentrations in skeletal muscle. In this case, it is apparent that OKG and glutamine act on different tissues . In rats implanted with a tumor, the administration of OKG (3.4-4.0 g/kg/day) for 5 days reduced muscle proteolysis by 33% while an isonitroge­no us amount of glycine had no effect.

In another animal model of trauma (bilateral femur fracture in the rat), there was no difference in body weight gain per gram of nitrogen intake after the administration of ornithine, OKG, or alpha-KG On the other hand, a study that compared OKG with arginine-a-ketoglutarate (AKG) suggested that the effects of OKG are not due to its a-KG content nor to its nitrogen content. That is, OKG produced a greater increase than AKG in muscle glutamine concentrations in burn injured rats. A decrease in intramuscular glutamine concentration is associated with skeletal muscle catabolism, thus, the action of OKG is neither solely related to its nitrogen content, nor to the presence of a-KG.

Human Studies

OKG has similarly been shown to have positive effects in humans on protein metabolism during hypercatabolic states. Vanbourdolle et al. 65 showed that the enteral (via the intestine) administration of OKG to burn patients improved glucose tolerance. In a study that compared varying doses of OKG (10, 20, and 30 g) delivered as one large bolus or via continuous infusion, investigators found that nitrogen balance improved and urinary 3-methylhistidine was reduced (an indicator of muscle protein degradation). In fact, the administration of 30 g as a bolus seemed to have the greatest benefit.

TPN supplemented with 0.35 g/kg of OKG to patients after elective abdominal surgery prevented the drop in protein synthesis seen in the unsupplemented controls. OKG supplementation might exert its anticatabolic effect via the maintenance of intramuscular glutamine levels. However, the mere provision of extra nitrogen does not confer similar effects. In a study that compared TPN supplemented with either OKG or branched-chain amino acids , there was less of a decrease in intramuscular glutamine levels in the OKG group Thus, one could argue that OKG administration is more effective than the BCAAs in reducing muscle glutamine loss and therefore ameliorating skeletal muscle proteolysis.

It is unclear if OKG exerts further anabolic/anticatabolic effects via alterations in the hormonal milieu. For instance, OKG administered to burn patients had no effect on plasma insulin or growth hormone concentration 65 On the other hand, OKG (15 g) given to growth-retarded prepubertal children produced an increase in plasma insulin-like growth factor-1 level.

Safety and Toxicity

High-dose OKG administration (up to 30 g/day) in humans has not been shown to have harmful side effects. It is not known if chronic ingestion (>6-12 months) has any deleterious effects.