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.