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Benefits of L-Ornithine

Evidence:Preliminary
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This content is for informational purposes only and does not constitute medical advice. Statements about dietary supplements have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease. Individual results may vary — consult your healthcare provider before starting any supplement. Full disclaimer

Evidence-Based Benefits

  • Ammonia detoxification — ornithine stimulates the urea cycle, accelerating ammonia-to-urea conversion and reducing blood ammonia levels during prolonged exercise (Sugino et al., 2008)
  • Exercise fatigue — a 2014 RCT found ornithine supplementation reduced perceived fatigue and improved energy during prolonged cycling, correlated with reduced blood ammonia (Demura et al., Clinical Nutrition)
  • Sleep quality — 400 mg ornithine before bed improved sleep quality and reduced morning cortisol in stressed Japanese workers (Miyake et al., 2014, Nutrition Journal, n=52)
  • Hepatic encephalopathy — L-ornithine-L-aspartate (LOLA) is an established treatment for hepatic encephalopathy (Butterworth & McPhail, 2019, meta-analysis)
  • Growth hormone release — ornithine at 12 g stimulated GH release in some studies, though the practical significance is debated (Bucci et al., 1990)

What the Research Says

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.

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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