Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects.

Abstract

Ornithine alpha-ketoglutarate (OKG) has been useful as an adjuvant of enteral and parenteral nutrition. However, its metabolism and mechanism of action remain unclear although it is known that alpha-ketoglutarate (alpha KG) and ornithine (ORN) follow, in part, common metabolic pathways. Six fasting healthy male subjects underwent three separate oral load tests: (i) they received 10 g of OKG (i.e., 3.6 g of alpha KG and 6.4 g of ORN); (ii) 6.4 g of ORN as ornithine hydrochloride, and (iii) 3.6 g of alpha KG as calcium alpha-ketoglutarate. Blood was drawn 15 times over a five-hour period for measurements of plasma amino acids, alpha KG, insulin, and glucagon. After OKG and ORN administration, plasma ORN peaked at 60-75 min (494 +/- 91 and 541 +/- 85 mumol/L). The increase in plasma alpha KG was very small. OKG, alpha KG, and ORN all increased glutamate concentrations at 60 min (mean: +43%, +68%, +68%, respectively, p less than 0.05 compared to basal values). However, only OKG increased proline and arginine levels at 60 min (mean: +35%, p less than 0.01 and mean: +41%, p less than 0.05). Furthermore, glutamate, proline, and arginine concentrations correlated linearly with ornithine levels at 60 min. Finally, OKG increased insulinemia and glucagonemia (mean: +24% at 15 min, p less than 0.05 and +30% at 60 min, p less than 0.01, respectively). These data provide evidence that the combination of ORN and alpha KG modifies amino acid metabolism in a way which is not observed when they are administered separately. In addition, the OKG-mediated increase in insulin levels probably does not appear to result from a direct action of ORN on pancreatic secretion.

The effect of L-ornithine hydrochloride ingestion on human growth hormone secretion after strength training

“…One of the reasons for this large difference is considered to be the different ornithine amounts ingested. Subjects ingested over 170 mg per kilogram of body mass in Bucci et al [10] and Cynober et al [9]'s study, who reported positive effect, but subjects ingested no more than 100mg per kilogram of body mass in the other studies. Moreover, subjects in all studies were mainly body builders or weight lifters who routinely conducted high intensity strength training.…”

“…Until now, arginine and ornithin have been mainly used to examine the effect on growth hormone secretion by oral amino acid ingestion [5][6][7][8][9][10]. However, there were mixed reports on the effect of growth hormone secretion by ornithine ingestion (negative reports: 5-9, Positive reports: 9, 10).…”

Anticatabolic activity of alpha-ketoglutaric acid in growing rats

“…Nevertheless, studies indicate that OKG administration improves gut morphology and function, and enhances intestinal adaptation under stress conditions (Dumas et al, 1998;Cynober, 1999). The positive action of the OKG on the gut would seem be due to the synergic effect exerted by its constituents (Cynober et al, 1990). This suggests that the simultaneous administration of Orn and AKG is necessary to obtain the same effects found with OKG.…”

Enteral Pancreatic-like Enzymes of Microbial Origin affect Insulin Release during an Intravenous Glucose Tolerance Test

“…It was found that AKG, as well as digestive enzymes, interacts with enterocytes and is involved in amino acid biosynthesis, offering advantages in a catabolic state and thus may also affect the rate of gluconeogenesis in mucosa cells [2,21,34,[36][37][38]. On the other hand, AKG in enterocytes undergoes amination and appears in the plasma as glutamate [36] which may stimulate insulin exocytosis from β-cells in response to glucose stimulation [39].…”