Overview
L-ornithine is a non-essential amino acid playing a central role in the urea cycle (ammonia detoxification) and serving as a precursor to arginine, citrulline, proline, and polyamines. While marketed heavily for growth hormone and athletic performance, ornithine's best-supported applications are stress-related sleep quality improvement and ammonia reduction during intense exercise.
Primary applications focus on sleep quality improvement (particularly under stress), athletic recovery and reduced perceived exertion, ammonia reduction during intense endurance exercise, potential liver support in hepatic encephalopathy (medical application), and often-overstated growth hormone enhancement claims.
Evidence quality is moderate for sleep quality benefits and athletic fatigue reduction, weak for growth hormone (requires impractical doses), good in clinical settings for ammonia-lowering applications.
Safety is excellent at typical doses (400-2000 mg daily) with minimal side effects, making ornithine one of the better-tolerated amino acid supplements.
What it means
Sleep and recovery amino acid that clears ammonia from your blood (reducing fatigue). Best evidence: improves sleep quality in stressed people at 400 mg. Reduces perceived effort during long workouts at 2-6 grams. Growth hormone hype is overblown - you'd need 40+ grams (expensive and causes diarrhea). Typical dose: 400-1000 mg for sleep, 2-6 grams for athletics.
Mechanisms and Evidence
What it means
Main job: urea cycle - converting toxic ammonia (from protein metabolism and exercise) into urea for peeing out. During intense exercise, ammonia accumulates causing fatigue.
Main metabolic role is urea cycle function - converting toxic ammonia into urea for excretion. During intense exercise or liver dysfunction, ammonia accumulates causing fatigue and cognitive impairment. Ornithine supplementation might reduce ammonia burden.
Arginine/NO precursor pathway: Ornithine converts to arginine (and then citrulline in a cycle), supporting nitric oxide production. This is indirect compared to direct arginine supplementation but creates sustained arginine availability.
Sleep Quality (Best Evidence)
For sleep quality, ornithine shows interesting benefits particularly in stressed individuals. Research found 400 mg ornithine before bed improved sleep quality, reduced time to fall asleep, lowered morning cortisol, and improved subjective fatigue symptoms the next day.
A study in stressed workers found 400 mg ornithine daily improved sleep quality and reduced cortisol. Sleep benefits appear more pronounced in those experiencing stress-related sleep disturbances rather than clinical insomnia.
What it means
The sleep sweet spot: 400 mg before bed if you're stressed. Works better for "stressed and can't sleep" than clinical insomnia. Lowers cortisol and improves next-day energy.
Athletic Recovery and Fatigue
For athletic recovery and fatigue, ornithine (2-6 grams around exercise) reduces perceived exertion during endurance exercise, lowers fatigue markers, and improves recovery in some studies. Benefits appear related to ammonia buffering during intense exercise. Effects are modest - not dramatic performance enhancement but reduced perceived effort and faster recovery.
What it means
Won't make you lift heavier or run faster, but 2-6 grams makes hard workouts feel less brutal and recovery faster. Especially good for long endurance stuff.
Growth Hormone (Overhyped)
For growth hormone, this is ornithine's most overstated application. While very high doses (40-170 mg/kg = 2.8-12 grams for 70kg person in IV studies, even higher orally) might increase growth hormone acutely, practical oral doses show minimal effect. Growth hormone marketing claims are largely unfounded at typical supplement doses.
What it means
GH marketing is BS at normal doses. You'd need 10-40+ grams for marginal GH increase - that's expensive and causes explosive diarrhea. Ignore GH claims.
Dosing and Forms
Dosing: 400-1000 mg before bed for sleep quality benefits. 2-6 grams daily for athletic recovery and ammonia buffering. 9-18 grams ornithine aspartate for clinical ammonia reduction (medical supervision). Start low (400-1000 mg) and assess response before increasing.
Forms: L-ornithine HCl or L-ornithine free form (most common for sleep and recovery), ornithine alpha-ketoglutarate (OKG - combined with alpha-ketoglutarate, used for wound healing and clinical applications), and ornithine aspartate (medical grade for hepatic encephalopathy).
Timing: Before bed for sleep benefits (30-60 minutes prior). Around exercise (before or during) for athletic applications. With or without food - no significant difference though empty stomach might improve absorption.
Safety
Safety is excellent. Minimal side effects at typical doses: GI upset or diarrhea (dose-dependent, usually above 10 grams), rare headache, and no serious adverse effects documented.
Contraindications: None well-established. Theoretical caution in: severe kidney disease (though ornithine is part of normal metabolism), and pregnancy/breastfeeding (limited data though likely safe as non-essential amino acid).
L-ornithine is a well-tolerated amino acid with moderate evidence for sleep quality and modest athletic recovery benefits, making it valuable for stress-related sleep issues and endurance training support, though growth hormone claims are overstated.
References
Miyake M, Kirisako T, Kokubo T, et al. Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers. Nutr J. 2014;13:53.
Sugino T, Shirai T, Kajimoto Y, Kajimoto O. L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism. Nutr Res. 2008;28(11):738-743.