Or8.5

Ornithine Research

40 peer-reviewed studies · Evidence score: 8.5/10

Aminoglycosides, vancomycin, and metronidazole for people with cirrhosis and hepatic encephalopathy

Jeyaraj R et al. • The Cochrane database of systematic reviews (2026)

Due to low- or very low-certainty evidence, we do not know if aminoglycosides benefit hepatic encephalopathy compared to placebo or other potentially active agents.

Aminoglycosides may increase mortality slightly compared to other potentially active agents (RR 1.64, 95% CI 1.03 to 2.62; I² = 0%; 3 studies, 166 participants).
The evidence was also very uncertain when comparing vancomycin to non-absorbable disaccharides (RR 0.94, 95% CI 0.26 to 3.40; I² not applicable; 2 studies, 72 participants), and metronidazole to other active agents (RR 0.97, 95% CI 0.14 to 6.66; I² = 0%; 3 studies, 242 participants).
Aminoglycosides may slightly increase the risk of serious adverse events compared with other potentially active agents (RR 1.60, 95% CI 1.03 to 2.47; I² = 0%; 3 studies, 166 participants).

Meta-Analysisn=1,405AI-discovered

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Metabolomics approaches for the early detection and therapeutics: type 2 diabetes-induced diabetic kidney disease-a systematic review and meta-analysis

Ramanathan G et al. • Metabolomics : Official journal of the Metabolomic Society (2025)

These identified metabolites hold potential as early markers for T2D-induced DKD.

These identified metabolites hold potential as early markers for T2D-induced DKD.
However, the use of these metabolites for clinical purposes requires experimental validation and clinical trials.
Further research warranted to confirm findings

Meta-Analysisn=2,024

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Nutritional interventions for preventing and treating pressure ulcers

Langer G et al. • The Cochrane database of systematic reviews (2024)

The benefits of nutritional interventions with various compositions for pressure ulcer prevention and treatment are uncertain.

Compared to standard diet, protein supplements may result in little to no difference in pressure ulcer incidence (protein 21 per 1000, standard diet 28 per 1000; RR 0.75, 95% CI 0.49 to 1.14; 4 studies, 4264 participants; low-certainty evidence).
The evidence is very uncertain about the gastrointestinal side effects of these supplements (protein 109 per 1000, standard diet 155 per 1000; RR 0.70, 95% CI 0.06 to 7.96; 2 studies, 140 participants, very low-certainty evidence).
Compared to standard diet, energy, protein and micronutrient supplements may slightly increase the number of healed pressure ulcers (energy, protein and micronutrients 366 per 1000, standard diet 253 per 1000; RR 1.45, 95% CI 1.14 to 1.85; 3 studies, 577 participants, low-certainty evidence).

Meta-Analysisn=7,920

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Comparative Efficacy of Treatment Options for Minimal Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis

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.

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.

Meta-Analysisn=1,563

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Neonatal mortality and outcome at the end of the first year of life in early onset urea cycle disorders--review and meta-analysis of observational studies published over more than 35 years

Burgard P et al. • Journal of inherited metabolic disease (2016)

UCDs, except for OTCDf, have high risks of EO disease manifestation and, except for ASLD, of neonatal death.

UCDs, except for OTCDf, have high risks of EO disease manifestation and, except for ASLD, of neonatal death.
No improvement of survival was observed over more than three decades.
Geographic variation remains to be explained.

Meta-Analysisn=1,542

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A systematic review to assess the impact of amino acids or their derivatives on skeletal muscle wasting in critically ill patients

Wittholz K et al. • Clinical nutrition (Edinburgh, Scotland) (2024)

Six trials have investigated the effect of enteral amino acid or amino acid metabolite supplementation on muscle mass in critically ill.

Six trials have investigated the effect of enteral amino acid or amino acid metabolite supplementation on muscle mass in critically ill.
The trial protocol is registered on PROSPERO (CRD42021275989).
Further research warranted to confirm findings

Systematic Reviewn=284

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Efficacy of L-ornithine L-aspartate for minimal hepatic encephalopathy in patients with cirrhosis: A meta-analysis of randomized controlled trials

He Q et al. • Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology (2024)

LOLA has significant beneficial effects on reversal of MHE and prevention of OHE in patients with cirrhosis compared with placebo or no intervention.

LOLA has significant beneficial effects on reversal of MHE and prevention of OHE in patients with cirrhosis compared with placebo or no intervention.
Further research warranted to confirm findings

Meta-Analysisn=292

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Safety assessment of L-ornithine oral intake in healthy subjects: a systematic review

Yang H et al. • Amino acids (2025)

This systematic-review examined the effects of Ornithine.

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.
Further research warranted to confirm findings

Systematic Review

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Effects of L-Ornithine Supplementation on Exercise Performance and Ammonia Metabolism: A Systematic Review

Miyake M et al. • Nutrients (2021)

L-Ornithine supplementation reduced plasma ammonia levels and subjective fatigue during prolonged exercise.

Reduced blood ammonia levels during and after prolonged exercise
Decreased subjective fatigue ratings in endurance activities
Optimal dosing appears to be 2-6g taken before exercise

Systematic Reviewn=240

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A systematic review and meta-analysis of nitric oxide-associated arginine metabolites in schizophrenia

Zinellu A et al. • Translational psychiatry (2024)

This meta-analysis examined the effects of Arginine.

In subgroup analysis, the pooled SMD for ornithine was significantly different in studies of untreated, but not treated, patients.
Our study suggests that DDAH1 and arginase are dysregulated in schizophrenia.
Further studies are warranted to investigate the expression/activity of these enzymes in the brain of patients with schizophrenia and the effects of targeted treatments.

Meta-Analysis

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Circulating arginine metabolites in Alzheimer's disease and vascular dementia: A systematic review and meta-analysis

Zinellu A et al. • Ageing research reviews (2023)

Alterations in ADMA, SDMA, and citrulline, biomarkers of NO synthesis, may be useful to investigate the pathophysiology of different forms of dementia and identify novel therapeutic strategies. (PROSPERO registration number: CRD42023439528).

By contrast, compared to controls, patients with dementia had significantly higher ADMA (standard mean difference, SMD=0.62, 95% CI 0.06-1.19, p = 0.029), SDMA (SMD=0.70, 95% CI 0.34-1.35, p<0.001), and citrulline concentrations (SMD=0.50, 95% CI 0.08-0.91, p = 0.018).
In subgroup analysis, the effect size was significantly associated with treatment with cholinesterase inhibitors and/or antipsychotics for ADMA, and underlying disorder (Alzheimer's disease), study continent, and analytical method for citrulline.
Alterations in ADMA, SDMA, and citrulline, biomarkers of NO synthesis, may be useful to investigate the pathophysiology of different forms of dementia and identify novel therapeutic strategies. (PROSPERO registration number: CRD42023439528).

Meta-Analysis

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Nutritional interventions in patients with burn injury: an umbrella review of systematic reviews and meta-analyses of randomised clinical trials

Naeini F et al. • The British journal of nutrition (2024)

Lower length of hospital stay was also seen in burn patients supplemented with glutamine, although the evidence was weak.

We adopted the random-effect models to determine the pooled effect sizes while employing the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to examine evidence certainty.
Glutamine showed a notable decrease in the length of hospital stay (MD: -6·23, 95 % CI: -9·53, -2·94, GRADE = low certainty).
However, other nutritional interventions, including combined immunonutrition, branched-chain amino acids, fish oil, ornithine α-ketoglutarate and trace elements, did not significantly affect the assessed clinical outcomes.

Meta-Analysis

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Serum Metabolome Analysis Identified Amino-Acid Metabolism Associated With Pain in People With Symptomatic Knee Osteoarthritis - A Cross-Sectional Study

Mehta O et al. • The journal of pain (2023)

PERSPECTIVE: Foreseeing the global burden of knee pain in Osteoarthritis (OA) and adverse effects of current pharmacological therapies, this study is envisaged to investigate serum metabolites and ...

PERSPECTIVE: Foreseeing the global burden of knee pain in Osteoarthritis (OA) and adverse effects of current pharmacological therapies, this study is envisaged to investigate serum metabolites and molecular pathways involved in knee pain.
The replicated metabolites in this study suggests targeting amino-acid pathways for better management of OA knee pain.

Meta-Analysis

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Arginine, Transsulfuration, and Folic Acid Pathway Metabolomics in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Zinellu A et al. • Cells (2023)

Our study suggests that the presence of significant alterations in metabolites within the arginine, transsulfuration, and folic acid pathways can be useful for assessing nitric oxide dysregulation and oxidative stress and identifying novel treatment targets in COPD. (PROSPERO registration number: CRD42023448036.).

Additionally, COPD was associated with significantly higher ADMA (SMD = 1.27, 95% CI 0.08 to 2.46, p = 0.037), SDMA (SMD = 3.94, 95% CI 0.79 to 7.08, p = 0.014), and ornithine concentrations (SMD = 0.67, 95% CI 0.13 to 1.22, p = 0.015).
In subgroup analysis, the SMD of homocysteine was significantly associated with the biological matrix assessed and the forced expiratory volume in the first second to forced vital capacity ratio, but not with age, study location, or analytical method used.
Further research warranted to confirm findings

Meta-Analysis

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Metabolomic Analysis of Respiratory Epithelial Lining Fluid in Patients with Chronic Obstructive Pulmonary Disease-A Systematic Review

Pulik K et al. • Cells (2023)

Metabolomics, by searching for biomarkers and distinguishing metabolic pathways, can allow us to understand the pathophysiology of COPD and the development of its phenotypes.

However, about 75% of smokers do not develop the disease despite the severe smoking burden.
Sphingolipids, phosphatidylethanolamines, and sphingomyelins distinguished COPD from non-smokers; volatile organic compounds, lipids, and amino acids distinguished COPD from smokers without the disease.
Five volatile organic compounds were correlated with eosinophilia and four were associated with a phenotype with frequent exacerbations.

Systematic Review

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Meta-Analysis of COVID-19 Metabolomics Identifies Variations in Robustness of Biomarkers

Onoja A et al. • International journal of molecular sciences (2023)

Whilst the studies reviewed here were small and may be subject to confounders, it is desirable that biomarker panels be resilient across cohorts if they are to find use in the clinic, highlighting the importance of assessing the robustness and reproducibility of metabolomics analyses in independent populations.

We further evaluate a crowdsourced panel comprising the COVID-19 metabolomics biomarkers most commonly mentioned in the literature between 2020 and 2023.
The best-performing panel in the independent dataset-measured by F1 score (0.76) and AUROC (0.77)-included nine biomarkers: lactic acid, glutamate, aspartate, phenylalanine, β-alanine, ornithine, arachidonic acid, choline, and hypoxanthine.
Panels comprising fewer metabolites performed less well, showing weaker statistical significance in the independent cohort than originally reported in their respective discovery studies.

Meta-Analysis

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Primary prevention of hepatic encephalopathy post-TIPS: A systematic review and meta-analysis

Liang A et al. • Medicine (2023)

In conclusion, a vast majority of medications were not found to be effective post-TIPS HE prophylaxis when used alone.

In conclusion, a vast majority of medications were not found to be effective post-TIPS HE prophylaxis when used alone.
A rifaximin and lactulose combination therapy may be beneficial.
Overall, there is significant limitation in the current data and more studies are needed to yield more robust meta-analysis results in the future.

Meta-Analysis

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Beneficial effects of L-ornithine L-aspartate for prevention of overt hepatic encephalopathy in patients with cirrhosis: a systematic review with meta-analysis

Butterworth RF • Metabolic brain disease (2020)

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.

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.

Meta-Analysisn=384

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Searching for biomarkers in schizophrenia and psychosis: Case-control study using capillary electrophoresis and liquid chromatography time-of-flight mass spectrometry and systematic review for biofluid metabolites

Kim S et al. • Neuropsychopharmacology reports (2022)

Neuropsychopharmacology Reports

Additionally, levels of fatty acids (15:0), (17:0), and (19:1), cis-11-eicosenoic acid, and thyroxine were significantly higher in patients with acute psychosis than in those in remission.
Moreover, we conducted a systematic review of comprehensive metabolomics studies on schizophrenia over the last 20 years and observed consistent trends of increase in some metabolites such as glutamate and glucose, and decrease in citrate in schizophrenia patients across several studies.
Hence, we provide substantial evidence for metabolic biomarkers in schizophrenia patients through our metabolomics study.

Systematic Review

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Lactulose Management of Minimal Hepatic Encephalopathy: A Systematic Review

Zucker DM et al. • Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates (2019)

Lactulose, probiotics, and L-ornithine-L-aspartate are a low-cost alternative compared with antibiotic treatment.

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.

Systematic Review

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