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Or8.5
Ornithine Research
Probably helpsHigh safety
25 peer-reviewed studies
What the evidence says
Probably helps
Ornithine helped in about half (3/5) of the studies that measured an effect — promising, but not unanimous.
Most evidence is from high-quality meta-analyses and randomised trials published 2007–2026 with a typical study size of 212 participants.
Based on 25 studies · 5 meta-analyses · 9 RCTs · 6,289 total participants
Confidence
High
What the studies found
3helped2didn't help· 20 more without graded effect data
Patients with cirrhosis and minimal hepatic encephalopathy2
Patients with overt hepatic encephalopathy2
Patients with cirrhosis and minimal HE1
Healthy subjects1
Active research area
16 studies in the last 5 years · Latest meta-analysis: 2024
200720162026
1Reversal of minimal hepatic encephalopathyMeta-AnalysisCited 62×n=1,563 · large study2020
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.
3Safety of L-ornithine oral intakeSystematic ReviewCited 1×2025
This systematic-review examined the effects of Ornithine.
Yang H et al. · Amino acids (2025)
The main observed adverse events were gastrointestinal disorders.
Indexing these adverse events, the no observed adverse effect level was estimated to be 12,000 mg/person/day for L-Orn in the form of L-Orn hydrochloride.
5Prevention of overt hepatic encephalopathyMeta-AnalysisCited 9×n=384 · medium study2020
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.
6Reduction of abnormal neuropsychiatric testsSystematic ReviewCited 8×2019
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.
L-ornithine-L-aspartate treatment may show a trend in superiority for clinical efficacy among standard interventions for OHE.
Zhu GQ et al. · Alimentary pharmacology & therapeutics (2015)
Noticeable benefit
← WorseNo effectBetter →
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.
8MASLD treatment outcomesSystematic Reviewn=1,671 · large study2026
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.
9Improvement of hepatic encephalopathyMeta-AnalysisCited 54×n=212 · medium study2009
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 harm
← 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.
10Improvement in grade of hepatic encephalopathyRCTCited 58×n=140 · medium study2022
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
Higher rates of improvement in grade of HE (92.5% vs. 66%, p < 0.001), lower time to recovery (2.70 ± 0.46 vs. 3.00 ± 0.87 days, p = 0.03), and lower 28-day mortality (16.4% vs. 41.8%, p = 0.001) were seen in the LOLA group as compared with placebo.
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.
12Gut microbiome and amino acid alterations in autismRCTCited 30×n=60 · small study2024
This rct examined the effects of Ornithine.
Chang X et al. · Scientific reports (2024)
Decreased ornithine levels and elevated valine levels may increase the risk of ASD through a metabolic pathway known as the nickel transport system.
The microbial metabolism in diverse environments was negatively correlated with phascolarctobacterium succinatutens.
Our study provides novel insights into compositional and functional alterations in the gut microbiome and metabolite profiles in ASD and the underlying mechanisms between metabolite and ASD.
14Management of hepatic encephalopathySystematic Review2026
Labenz C · Deutsche medizinische Wochenschrift (1946) (2026)
Nutritional recommendations are a key component of therapy, especially to prevent sarcopenia.
In cases of refractory HE or recurrent relapses despite guideline-based treatment, liver transplantation should always be considered.
In general, early detection and individualized management of HE is essential to preserve and improve quality of life, prognosis, and functional independence of the affected patients.Thieme.
Zhang H, Fu Y, Lin M, Nan Z, Zhao D. · Frontiers in medicine (2025)
Large harm
← WorseNo effectBetter →
Likely real
Meta-analysis results: In terms of the total effective rate (RR: 1.31, 95%CI: 1.22, 1.42), the result is statistically significant ( Z = 7.15, P = 0.00001 < 0.05), and for AST, ALT, NH3, TBIL, P = 0.00001 < 0.05.
The pooled (RR: 1.31 [95% CI = 1.22, 1.42]), which is statistically significant, LOLA and Lactulose is 31% more effective than Lactulose alone in the control group in treating HE.
Conclusion This study indicates that the combination of LOLA and lactulose in the treatment of hepatic encephalopathy has a higher total effective rate in clinical practice and can significantly reduce the levels of AST, ALT, TBIL, and NH3.
16Efficacy comparison of treatments for overt hepatic encephalopathyRCTn=252 · medium study2025
Released to the public on 26 June 2025.
Shahbaz A, Jamil Q, Iqbal SM, Jamil MN, Khan JA, Aufy M. · Trials (2025)
Background Pakistan has a high prevalence of HCV and HBV, causing cirrhosis, leading to hepatic encephalopathy in approximately 30-45% of cirrhotic patients.
The secondary outcome is to determine the length of hospital stay and recovery time (days), monitoring of adverse drug reactions and death by cause in OHE patients.
Discussion This randomized controlled trial protocol will compare the efficacy of four proposed groups of medications to fill the gap in current knowledge.
Then, we describe possible links between polyamines and various neurological disorders, and finally the possible therapeutic implications on targeting the polyamine system for the treatment of various disorders were proposed.
This review may provide an up-to-date overview to propose the new perspective about targeting PA for developing potential therapeutic strategies.
Our results show that L-arginine can restrain crypt cell hyperproliferation and the expression of survivin, an inhibitor of apoptosis protein.
Ma Q et al. · Clinical cancer research : an official journal of the American Association for Cancer Research (2007)
Our results show that L-arginine can restrain crypt cell hyperproliferation and the expression of survivin, an inhibitor of apoptosis protein.
This suggests that L-arginine can block the formation and development of colorectal tumors, and this effect might be related to the increased serum NO concentration and decreased ODC activity.