L-ornithine

What it is

Ornithine is one of the amino acids that are not incorporated into protein. The body produces it itself; it occurs in foods only in small amounts, and meat and fish are not rich in it. It performs its main task in the liver: in the urea cycle, ammonia, a toxic waste product of protein metabolism, is converted into urea and excreted via the kidneys. Ornithine is both starting material and activator in this process.

As a preparation there are two forms that are legally separate. L-ornithine, usually as the hydrochloride, is sold as a food supplement. L-ornithine L-aspartate, LOLA for short, combines ornithine with the amino acid aspartate and is approved in Germany as a medicine for the treatment of hepatic encephalopathy, a brain dysfunction caused by too much ammonia in severe liver disease. The data on the medicine come almost entirely from people with liver cirrhosis and cannot simply be transferred to healthy people.

How it is supposed to work

The basic idea is simple: more ornithine is supposed to drive the urea cycle and break down ammonia faster. With a diseased liver, this makes sense. According to the summary of product characteristics, LOLA acts on two pathways of ammonia detoxification, urea synthesis and glutamine synthesis. The same summary of product characteristics, however, states that under normal conditions ornithine and aspartate are not the limiting factor for urea synthesis. So with a healthy liver, the raw material is usually not what is missing.

For athletes, the hope behind it is that less ammonia during hard exertion means less fatigue. For everyday life, ornithine is advertised as a remedy for stress and for better sleep, because it dampened the stress response in animal experiments. Older promises from the bodybuilding scene revolve around the release of growth hormone.

What users are looking for

Many reach for ornithine when they find it hard to switch off in the evening, do not feel rested in the morning, or want to do something for their liver after a long night. Athletes hope for less exhaustion. The studies measure exactly such subjective improvements, and these vary from person to person. Anyone who tries it is best off keeping a simple sleep and fatigue diary for a few weeks.

What the studies show

Cochrane review on LOLA in liver cirrhosis, 2018

The authors analysed data from 29 randomized trials with 1,891 people with cirrhosis. Calculated across all trials, LOLA lowered the risk of encephalopathy and death. In the few trials with low risk of bias, the effect disappeared, and the quality of the evidence was rated as very low. Compared with lactulose and rifaximin, the standard agents, no difference was found.

Ornithine for stress and sleep

52 healthy Japanese working adults who felt mildly stressed and tired took 400 mg of L-ornithine per day or placebo for 8 weeks. In the ornithine group, serum cortisol and the ratio of cortisol to DHEA-S fell, anger declined, and participants rated their sleep as better. Sleep quality was recorded by questionnaire, not in a sleep laboratory.

Ornithine in exercise without an ammonia effect

In a crossover study, 16 young men took tea catechins with ornithine or placebo, once and over 14 days. Neither the ammonia level during 60 minutes of cycling nor performance in the subsequent 15-minute test differed. The exertion, however, felt less strenuous with the preparation.

Where the data stop

The studies in healthy people are small, with 17 to 65 participants, come predominantly from Japan and mainly measure subjective variables such as fatigue, mood and perceived sleep. On cortisol they contradict each other: in the eight-week study it fell, in the stress test study it remained unchanged. The hope that ornithine lowers ammonia during exercise was not confirmed in a controlled study, and according to the authors a performance advantage in maximal sprints could not be explained by ammonia.

The growth hormone narrative rests on a study with 17 athletes who took ornithine together with arginine. That ornithine releases insulin was not confirmed in 12 bodybuilders. For the medicine LOLA, the benefit remains uncertain despite many trials, because the effect was not seen in the methodologically best trials. For fatty liver, there are first positive liver values from 3 randomized trials; large randomized trials are lacking. For ornithine as a remedy after alcohol, there are no reliable human data.

Status, approval and legal

In Germany, ornithine has two separate roles. As a food supplement, the BVL (Federal Office of Consumer Protection and Food Safety) permitted capsules with L-ornithine from other EU states by general ruling in 2014, with a maximum of 500 mg per capsule at 2 capsules daily. A separate general ruling for L-ornithine L-aspartate as a food supplement is not known. As a medicine, L-ornithine L-aspartate is approved, pharmacy-only, under the name Hepa-Merz for the treatment of latent and manifest hepatic encephalopathy, with up to 1 to 2 sachets of 3.0 g three times daily. Food supplements may not be advertised for the treatment of liver diseases. Ornithine is not on the 2026 WADA Prohibited List.

Safety

Ornithine is well tolerated. In 22 studies with healthy people, lasting up to 156 days, gastrointestinal complaints were the most important side effect, and the risk did not differ from placebo. The summary of product characteristics of the medicine lists occasional nausea, vomiting, stomach pain, flatulence and diarrhoea, and very rarely limb pain. LOLA is contraindicated in more severe kidney dysfunction, should be avoided during pregnancy and breastfeeding, and there are no data for children. The granules contain fructose and are unsuitable in hereditary fructose intolerance. Anyone with liver or kidney disease should therefore clarify intake with a physician instead of self-treating. In the rare hereditary disease gyrate atrophy, ornithine levels are already greatly elevated; additional ornithine is not something to take on one’s own there.

Sources

• Goh et al., Cochrane Database Syst Rev 2018 – L-ornithine L-aspartate in hepatic encephalopathy
• Miyake et al., Nutr J 2014 – L-ornithine, stress markers and sleep quality
• Moriyasu et al., J Clin Med 2024 – L-ornithine and social stress
• Sugino et al., Nutr Res 2008 – L-ornithine and physical fatigue
• Nagayama et al., Eur J Appl Physiol 2025 – catechins and ornithine, ammonia and performance
• Yang et al., Amino Acids 2025 – safety of oral L-ornithine, systematic review
• Miura et al., Amino Acids 2023 – tolerability of increasing ornithine doses
• Zajac et al., J Strength Cond Res 2010 – arginine and ornithine, growth hormone
• Summary of product characteristics (Fachinformation) Hepa-Merz Granulat 3000
• BVL – general ruling (Allgemeinverfügung) on food supplements with L-ornithine, 2014