Supplement

Ornithine

L-ornithine (clinical form: L-ornithine-L-aspartate)

Evidence TierCWADA NOT PROHIBITED

tuneTypical Dose

400-1000 (wellness), higher protocolized doses in medical LOLA care

watchEffect Window

Days-weeks for stress/sleep outcomes. Clinical HE effects depend on treatment regimen and disease status.

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

Ornithine is an amino acid or related metabolite involved in protein turnover and cellular signaling. It is taken to support exercise performance, recovery, or specific metabolic pathways.

Evidence is context dependent. Trials most often evaluate exercise outcomes such as fatigue, blood flow, or muscle soreness, and some show small benefits at adequate doses. Minority uses include support for wound healing, immune function, and sleep quality. Effects vary with baseline protein intake, training status, and coingested nutrients.

Urea-cycle amino acid support with ammonia-related metabolic effects. Possible stress-response modulation in low-dose wellness studies.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Clinical HE support in medical contexts (LOLA)
  • Modest stress/sleep improvement signal in small healthy-adult trials

Secondary Outcomes

  • Mixed exercise-fatigue/performance findings
  • Context-dependent utility (medical vs wellness)

Safety

Contraindications and Interactions

Contraindications

  • Unsupervised use for severe liver disease symptoms
  • Significant renal dysfunction without clinician input
  • Pregnancy/lactation without guidance

Side effects

  • Mild GI discomfort
  • Occasional headache
  • Potential intolerance at higher doses

Interactions

  • Complex liver-regimen polypharmacy contexts
  • Multi-amino-acid stacks increasing GI load
  • Sedative stacks confounding sleep outcomes

Avoid if

  • Self-treatment of hepatic encephalopathy
  • Severe liver/kidney disease without supervision
  • Inability to track objective response

Evidence

Study-level References

ornithine-SRC-001Meta-analysis.
Sourceopen_in_new

Butterworth RF et al. Hepatology. 2018;67(2):700-710. PMID: 28659265.

Population: Patients with hepatic encephalopathy/liver disease.

Dose protocol: L-ornithine-L-aspartate clinical regimens (oral/IV across trials).

Key findings: Pooled evidence supports HE outcome improvement versus control.

Notes: Trial heterogeneity and variable quality across included studies.

Paper content

Pooled evidence supports HE outcome improvement versus control.

ornithine-SRC-002Randomized, placebo-controlled study.
Sourceopen_in_new

Miyake M et al. Nutr J. 2014;13:53. PMID: 25757466.

Population: Healthy workers with stress/fatigue complaints.

Dose protocol: L-ornithine 400 mg/day (short-term).

Key findings: Improved sleep quality/stress-related outcomes versus placebo.

Notes: Small sample and subjective outcome reliance.

Paper content

Improved sleep quality/stress-related outcomes versus placebo.

ornithine-SRC-003Randomized, placebo-controlled trial.
Sourceopen_in_new

Muthaiyah B et al. Front Nutr. 2023;9:1042960. PMID: 36724761.

Population: Healthy workers with stress/sleep concerns.

Dose protocol: Microencapsulated L-ornithine supplementation for 8 weeks.

Key findings: Favorable stress/sleep improvement signal versus placebo.

Notes: Single-trial context and modest sample.

Paper content

Favorable stress/sleep improvement signal versus placebo.

ornithine-SRC-004Randomized crossover-style exercise trial context.
Sourceopen_in_new

Demura S et al. J Nutr Sci Vitaminol (Tokyo). 2010;56(2):136-141. PMID: 19335716.

Population: Healthy adults in exercise-related protocol.

Dose protocol: Oral ornithine intervention with exercise outcomes.

Key findings: Mixed effects on fatigue/biomarkers with no robust performance conclusion.

Notes: Older, small, exercise-specific design.

Paper content

Mixed effects on fatigue/biomarkers with no robust performance conclusion.

ornithine-SRC-005Systematic review and meta-analysis of randomized controlled trials.
Sourceopen_in_new

He, Mao, Chen, Zeng, Deng, Hu. Efficacy of L-ornithine L-aspartate for minimal hepatic encephalopathy in patients with cirrhosis: A meta-analysis of randomized controlled trials. Arab J Gastroenterol. 2024;25(2):116-123. doi:10.1016/j.ajg.2024.01.006. PMID:38403493.

Population: Patients with cirrhosis and minimal hepatic encephalopathy.

Dose protocol: LOLA oral or IV across 6 RCTs in cirrhosis with minimal HE.

Key findings: LOLA reversed minimal HE (RR 2.264) and reduced progression to overt HE (RR 0.220). Oral LOLA showed stronger effects.

Notes: Updates the earlier 2017 meta-analysis with focus on minimal/subclinical HE specifically.

Paper content

This meta-analysis pooled 6 RCTs (292 patients) evaluating LOLA for minimal hepatic encephalopathy in cirrhosis. LOLA was significantly more effective at reversing minimal HE (RR 2.264) and reducing progression to overt HE (RR 0.220). Oral LOLA showed stronger effects than intravenous administration. Ammonia reduction and mortality did not differ significantly. The analysis updates and strengthens the evidence base for LOLA in the early, subclinical stage of hepatic encephalopathy, supporting its use as a medical intervention in cirrhosis management.

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