[Physiological functions of L-ornithine and L-aspartate in the body and the efficacy of administration of L-ornithine-L-aspartate in conditions of relative deficiency]

Abstract

L-ornithine-L-aspartate (LOLA) is a stable salt of two natural nonessential L-amino acids: ornithine and aspartic acid. It is formulated and marketed in low and high doses. Low doses are used as a food supplement and high doses (above 5 g) as a medicinal product to lower blood ammonia concentration and to eliminate symptoms of hepatic encephalopathy associated with liver cirrhosis. The aim of this review is to present physiological roles of L-ornithine and L-aspartate in the human body, to assess conditions under which these amino acids could be deficient, to analyze consequences of these deficiencies, and to review the current state of knowledge on the effects of LOLA administration. The data used in this publication result from searches of different electronic databases such as Cochrane Trials Register, MEDLINE, PubMed, Medscape, or Google Scholar, with a cut-off date of November 29, 2009, using terms: L-ornithine-L-aspartate, ornithine aspartate, ornithine, Hepa-Merz, ornithine deficiency, hyperammonemia, hepatic encephalopathy, and liver cirrhosis. Both amino acids play key roles in ammonia detoxification and in proline and polyamine biosyntheses. Polyamines are considered critical for DNA synthesis and cell replication and have been shown to stimulate hepatic regeneration. Supplementation with ornithine in animal models demonstrated enhanced wound breaking strength and collagen deposition. It has been shown in vitro, in vivo and in perfused organs that urea synthesis from ammonia is limited by endogenous ornithine and that ornithine can pharmacologically promote urea formation to a greater degree than any ammonia supply. Administration of LOLA in high doses reduced high blood ammonia induced either by ammonium chloride or protein ingestion or existing as a clinical complication of cirrhosis. In health and with proper diet, L-ornithine and L-aspartate are synthesized de novo in sufficient quantities, but in the states of disease, tissue damage, organ insufficiency, excessive metabolic demand, growth, pregnancy, or urea cycle enzyme deficiencies, these amino acids need to be supplemented with the food. The review of available data indicate that there is direct and indirect (resulting from physiology) scientific rationale for dietary use of LOLA, depending on an individual's physiological, metabolic or pathological conditions. In conditional ornithine deficiency, daily supplementation with LOLA at doses about 1 g/day is safe and, as demonstrated in vitro, should be sufficient to saturate tissue ornithine concentration to prevent postprandial hyperammonemia and to stimulate tissue regeneration.