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Or5.0
Ornithine Research
Likely helps
29 peer-reviewed studies
What the evidence says
Likely helps
Ornithine appears to help in 4 of 4 studies with measurable effects — the evidence leans clearly favourable.
Most evidence is from high-quality meta-analyses and randomised trials published 1989–2026 with a typical study size of 140 participants.
Based on 29 studies · 5 meta-analyses · 18 RCTs · 2,757 total participants
Patients with cirrhosis and minimal hepatic encephalopathy2
Patients with overt hepatic encephalopathy2
Patients with cirrhosis and minimal HE1
Healthy subjects1
Active research area
11 studies in the last 5 years · Latest meta-analysis: 2024
198920072026
1Reversal of minimal hepatic encephalopathyMeta-AnalysisCited 6×n=292 · medium study2024
In plain English: LOLA has significant beneficial effects on reversal of MHE and prevention of OHE in patients with cirrhosis compared with placebo or no intervention.
He Q et al. · Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology (2024)
Meta-analysis of 6 randomised trials in 292 patients with cirrhosis and minimal hepatic encephalopathy, L-ornithine L-aspartate (LOLA) against placebo or no treatment.
LOLA reversed minimal encephalopathy more often (RR 2.26, 95% CI 1.53 to 3.35) and reduced progression to overt encephalopathy (RR 0.22, 95% CI 0.08 to 0.64).
It did not reduce mortality (RR 0.42, 95% CI 0.06 to 2.77) or ammonia levels.
2Reversal of minimal hepatic encephalopathyMeta-AnalysisCited 66×n=1,563 · large study2020
In plain English: In a meta-analysis of data from 25 trials, we found rifaximin and lactulose to be most effective for reversal of minimal HE in patients with cirrhosis.
Dhiman RK et al. · Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (2020)
In a meta-analysis of data from 25 trials, we found rifaximin and lactulose to be most effective for reversal of minimal HE in patients with cirrhosis.
L-ornithine L-aspartate and lactulose are most effective in the prevention of overt HE.
Lactulose was the only agent that was effective in reversing minimal HE, preventing overt HE, reducing ammonia, and improving quality of life, with tolerable adverse effects.
4Prevention of overt hepatic encephalopathyMeta-AnalysisCited 9×n=384 · medium study2020
In plain English: These findings provide the first direct evidence of potential benefit of LOLA for the prevention of OHE in cirrhosis across a range of clinical presentations.
Butterworth RF · Metabolic brain disease (2020)
Huge benefit
← WorseNo effectBetter →
Likely real
Treatment with LOLA resulted in significant reductions in the risk of progression to OHE in MHE patients (3 studies) with RR: 0.23 [95% CI: 0.07, 0.73], p < 0.01.
OHE prevention/prophylaxis was accompanied by significant reductions of blood ammonia.
Both oral and intravenous formulations of LOLA appeared to be effective for the prevention of progression to OHE in patients with MHE.
In addition, L-ornithine-L-aspartate (MD -20.18, 95% CI -40.12 to -0.27) provided a significant reduction in blood ammonia concentration compared with observation.
L-ornithine-L-aspartate treatment may show a trend in superiority for clinical efficacy among standard interventions for OHE.
Rifaximin shows the greatest reduction in blood ammonia concentration, and treatment with neomycin demonstrates a higher probability in causing adverse effects among the five compared interventions.
6Reduction of abnormal neuropsychiatric testsSystematic ReviewCited 8×2019
In plain English: Lactulose, probiotics, and L-ornithine-L-aspartate are a low-cost alternative compared with antibiotic treatment.
Zucker DM et al. · Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates (2019)
Treatment of minimal hepatic encephalopathy with lactulose, probiotics, or L-ornithine-L-aspartate was seen to be equally effective in reducing abnormal tests at 1, 3, and 12 months post-treatment.
All patients with minimal hepatic encephalopathy should be screened using a neuropsychiatric test and receive treatment as needed.
Treatment can delay or eliminate risky automobile accidents and harm to self.
In plain English: Preclinical evidence suggests that LOLA exerts pleiotropic hepatoprotective effects in MASLD by targeting hyperammonemia-induced fibrosis and metabolic dysregulation.
Ismaiel A et al. · European journal of clinical investigation (2026)
In clinical studies, results from three randomized controlled trials (RCTs) indicated significant improvements in liver enzymes (ALT, AST) and lipid profiles, with reductions in hepatic steatosis.
Evidence from six observational and open-label studies corroborated these biochemical improvements and further demonstrated significant reductions in blood ammonia levels, improved intrahepatic microcirculation and reduced liver stiffness and patient-reported fatigue.
Preclinical evidence suggests that LOLA exerts pleiotropic hepatoprotective effects in MASLD by targeting hyperammonemia-induced fibrosis and metabolic dysregulation.
8Improvement of hepatic encephalopathyMeta-AnalysisCited 54×n=212 · medium study2009
In plain English: LOLA benefited patients with overt hepatic encephalopathy (I or II), whereas these data do not support the use of LOLA for patients with subclinical hepatic encephalopathy.
Jiang Q et al. · Journal of gastroenterology and hepatology (2009)
Huge benefit
← WorseNo effectBetter →
Likely real
LOLA versus placebo had a significant effect on improvement of hepatic encephalopathy (relative risk 1.89; 95% CI 1.32 to 2.71; P = 0.0005).
This comparison showed no statistical heterogeneity (P = 0.85 and chi(2) = 0.09).
LOLA benefited patients with overt hepatic encephalopathy (I or II), whereas these data do not support the use of LOLA for patients with subclinical hepatic encephalopathy.
9Improvement in grade of hepatic encephalopathyRCTCited 65×n=140 · medium study2022
In plain English: Combination of LOLA with lactulose and rifaximin was more effective than only lactulose and rifaximin in improving grades of HE, recovery time from encephalopathy, with lower 28-day mortality.
Jain A et al. · Hepatology (Baltimore, Md.) (2022)
Huge benefit
← WorseNo effectBetter →
Likely real
Double-blind RCT in 140 patients with cirrhosis and grade III to IV hepatic encephalopathy, given intravenous LOLA 30 g over 24 hours for 5 days or placebo, on top of lactulose and rifaximin.
Encephalopathy grade improved in 92.5% with LOLA vs 66% with placebo (p < 0.001), and recovery was faster (2.70 vs 3.00 days).
28-day mortality was lower with LOLA (16.4% vs 41.8%, p = 0.001). This was intravenous treatment in hospital, not an oral supplement.
In plain English: Serum cortisol levels and the cortisol/DHEA-S ratio were significantly decreased in the L-ornithine group in comparison with the placebo group.
Miyake M et al. · Nutrition Journal (2014)
Fifty-two healthy Japanese adults were randomised to L-ornithine (400 mg/day) or placebo for 8 weeks.
Serum cortisol levels and the cortisol/DHEA-S ratio were significantly decreased in the L-ornithine group compared with placebo.
Anger was reduced and perceived sleep quality was improved in the L-ornithine group.