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L-Ornithine Research & Evidence

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Evidence Level

Preliminary

L-Ornithine is an amino acid integral to the urea cycle and has been extensively studied for its therapeutic applications. A systematic review by Butterworth et al. (2020) involving six randomized controlled trials (RCTs) with 384 participants demonstrated that L-ornithine L-aspartate (LOLA) significantly reduced the risk of overt hepatic encephalopathy progression compared to placebo or no intervention. Similarly, He et al. (2024) conducted a meta-analysis of six RCTs involving 292 patients and reported that LOLA improved minimal hepatic encephalopathy reversal with a relative risk of 2.264 and reduced overt progression with a relative risk of 0.220.

In the context of exercise performance, Sugino et al. (2008) demonstrated that L-ornithine supplementation attenuated physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism. Additionally, Miyake et al. (2014) found that a low dose of 400 mg of L-ornithine improved sleep quality in healthy workers.

Despite these findings, larger-scale RCTs are needed to confirm the exercise performance benefits and further establish the efficacy of L-ornithine across diverse applications.

Evidence by Condition

ConditionStudied DoseEvidence
Exercise fatigue2-6 g before prolonged exercisePreliminary
Sleep quality400 mg before bedPreliminary
Hepatic encephalopathy (LOLA)9-18 g/day L-ornithine-L-aspartateStrong

References

  1. RCTMiyake M, Kirisako T, Kokubo T, et al. (2014). Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers. Nutrition Journal. DOI PubMed
  2. RCTSugino T, Shirai T, Kajimoto Y, Kajimoto O. (2008). L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism. Nutrition Research. DOI PubMed
  3. Butterworth RF, McPhail MJ. (2019). L-Ornithine L-Aspartate (LOLA) for Hepatic Encephalopathy in Cirrhosis: Results of Randomized Controlled Trials and Meta-Analyses. Drugs. DOI PubMed
  4. Meta-analysisHe Q, Mao C, Chen Z, Zeng Y, et al. (2024). Efficacy of L-ornithine L-aspartate for minimal hepatic encephalopathy in patients with cirrhosis: A meta-analysis of randomized controlled trials.. Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology. DOI PubMed
  5. Meta-analysisButterworth RF (2020). Beneficial effects of L-ornithine L-aspartate for prevention of overt hepatic encephalopathy in patients with cirrhosis: a systematic review with meta-analysis.. Metabolic brain disease. DOI PubMed
  6. Meta-analysisGoh ET, Stokes CS, Sidhu SS, Vilstrup H, et al. (2018). L-ornithine L-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis.. The Cochrane database of systematic reviews. DOI PubMed
  7. Bai M, Yang Z, Qi X, Fan D, et al. (2013). l-ornithine-l-aspartate for hepatic encephalopathy in patients with cirrhosis: a meta-analysis of randomized controlled trials.. Journal of gastroenterology and hepatology. DOI PubMed
Show 5 more references
  1. Jiang Q, Jiang XH, Zheng MH, Chen YP (2009). L-Ornithine-l-aspartate in the management of hepatic encephalopathy: a meta-analysis.. Journal of gastroenterology and hepatology. DOI PubMed
  2. Ismaiel A, Ciornolutchii V, Popa SL, Dumitrascu DL (2026). Can ammonia scavenging treat MASLD? Evaluating the evidence for L-ornithine L-aspartate-A systematic review.. European journal of clinical investigation. DOI PubMed
  3. Yang H, Kuramochi Y, Sato S, Sakai R, et al. (2025). Safety assessment of L-ornithine oral intake in healthy subjects: a systematic review.. Amino acids. DOI PubMed
  4. Zhang H, Fu Y, Lin M, Nan Z, et al. (2025). Efficacy and safety of L-ornithine L-aspartate combined with lactulose in treatment of hepatic encephalopathy: a systematic review and meta-analysis of randomized controlled trial.. Frontiers in medicine. DOI PubMed
  5. Shynkevych VI, Kolomiiets SV, Udaltsova KO, Kaidashev IP (2025). L-ornithine supplementation in periodontitis treatment yields greater benefits than L-arginine after one year: Part II of a randomized controlled pilot study.. Complementary therapies in medicine. DOI PubMed