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L-ornithine

Urea cycle amino acid, adjunct for hyperammonaemia

ATC code: A16AA-L-ORNITHINE

Brand names – supplements: NOW Foods L-Ornithine, Solgar L-Ornithine, Doctor's Best L-OrnithineSupplements are not tested in clinical trials and are not registered as medications.

Updated · Methodology

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

D

Fatigue and low energy (supplement marketing)

Not recommended

L-ornithine is an amino acid marketed in supplements for fatigue, energy, and better sleep. Direct evidence is thin and comes from a few small trials in healthy volunteers. In Miyake et al. (2014, n=52, 400 mg/day for 8 weeks) subjective sleep quality improved and the cortisol/DHEA-S ratio fell, yet fatigue on most POMS subscales did not change; earlier small studies by Sugino (2008, n=17) and Demura (2011, n=10) reported less subjective fatigue after exercise in tiny samples. did not substantiate any benefit claim for L-ornithine, judging the submitted data insufficient, and the amino acid appears in no international guideline for fatigue or sleep disorders. No harm is documented at usual doses, so this pair sits at tier D: benefit unproven, net-negative not established.

Sources

  1. Nutrition Research: L-Ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism (2008)
  2. European Journal of Applied Physiology: Effect of L-ornithine hydrochloride ingestion on intermittent maximal anaerobic cycle ergometer performance and fatigue recovery after exercise (2011)
  3. EFSA: Scientific Opinion on the substantiation of health claims related to L-ornithine (2011)
  4. Nutrition Journal: Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers (2014)

ICD-10: R53 · ICD-11: MG22

D

Muscle mass gain (bodybuilding self-use)

Not recommended

L-ornithine is marketed as a supplement that raises growth hormone and helps build muscle. A single large dose (around 170 mg per kg of body weight) can briefly raise blood growth hormone and IGF-1, but the rise is short-lived and does not translate into real gains in muscle size or strength. Controlled trials and sports-nutrition reviews have not shown an ergogenic effect in people who train. The European authority has not approved any claim that L-ornithine benefits muscle or physical performance, and a shift in a single hormone marker does not substantiate such a claim. For gaining muscle, resistance training and adequate protein intake are the reliable approach, not L-ornithine.

Sources

  1. Journal of Strength and Conditioning Research: Arginine and ornithine supplementation increases growth hormone and insulin-like growth factor-1 serum levels after heavy-resistance exercise in strength-trained athletes (2010)
  2. Amino Acids: Safety assessment of L-ornithine oral intake in healthy subjects: a systematic review (2025)
  3. EFSA Journal 2018;16(10):e05434 (EFSA NDA Panel): Guidance on the scientific requirements for health claims related to muscle function and physical performance (Revision 1) (2018)
  4. EFSA: Scientific Opinion on the substantiation of health claims related to L-ornithine (2011)
  5. Nutrition: Use of amino acids as growth hormone-releasing agents by athletes (2002)
D

Weight loss

Not recommended

L-ornithine is heavily marketed on iHerb and in sports shops as a fat burner and energy aid through effects on the urea cycle, creatine synthesis and growth hormone release. assessed the proposed L-ornithine claim in 2011 (opinion 2251, contribution to metabolism via the urea cycle) and gave an unfavourable opinion: no causal relationship was established. There is no authorised L-ornithine claim on fat loss or muscle gain. There are no high-quality weight loss RCTs in healthy subjects. The standard is dietary control, physical activity and, when indicated, pharmacological or bariatric care. If weight loss matters, discuss the plan with an endocrinologist or dietitian and consider a second opinion before buying L-ornithine for this purpose.

Sources

  1. EFSA: Scientific Opinion on the substantiation of health claims related to L-ornithine (2011)
How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Ornithine participates in the urea cycle, the body's main pathway for ammonia disposal. Combined with aspartate it forms L-ornithine-L-aspartate (LOLA), which activates ornithine transcarbamylase and promotes ammonia conversion into urea in hepatocytes and into glutamine in perivenous hepatocytes and muscle. This mechanism underlies LOLA use in hepatic encephalopathy. Free L-ornithine as monotherapy is less studied; oral bioavailability is lower than for the aspartate combination.

Safety

Contraindications

  • Hypersensitivity to ornithine
  • Severe renal failure (creatinine above 3 mg/dL)
  • Inherited urea cycle disorders

Serious adverse effects

  • Worsening hyperammonaemia in inherited urea cycle defects
  • Allergic reactions

Common adverse effects

  • Nausea and abdominal pain
  • Diarrhoea at doses above 6 g/day
  • Headache

Pregnancy: can you take L-ornithine?

Safety of pharmacological doses in pregnancy has not been studied. In hepatic encephalopathy during pregnancy the hepatologist and obstetrician decide on LOLA.

Breastfeeding: can you take L-ornithine?

Compatible. Ornithine is present in human milk and dietary protein. Therapeutic doses in a lactating woman with hepatic encephalopathy are assessed individually.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

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Frequently asked

What is L-ornithine used for?

L-ornithine is evaluated for the following indications with varying evidence strength: Weight loss (evidence tier D), Muscle mass gain (bodybuilding self-use) (evidence tier D), Fatigue and low energy (supplement marketing) (evidence tier D). See the full indication matrix with dosing and citations above on this page.

What are the side effects of L-ornithine?

Common side effects of L-ornithine (≥ 1 in 100): Nausea and abdominal pain, Diarrhoea at doses above 6 g/day, Headache. See the Safety section for uncommon and serious reactions.

Is L-ornithine safe during pregnancy?

Safety of pharmacological doses in pregnancy has not been studied. In hepatic encephalopathy during pregnancy the hepatologist and obstetrician decide on LOLA.

Is L-ornithine compatible with breastfeeding?

Compatible. Ornithine is present in human milk and dietary protein. Therapeutic doses in a lactating woman with hepatic encephalopathy are assessed individually.

Who should not take L-ornithine?

L-ornithine is contraindicated in: Hypersensitivity to ornithine; Severe renal failure (creatinine above 3 mg/dL); Inherited urea cycle disorders. Full list in the Safety section.

Other drugs in this group

L-theanine, L-tyrosine, Licorice root (Glycyrrhiza glabra, root and rhizome; including deglycyrrhizinated DGL), Lion's Mane Mushroom (Hericium erinaceus), Medium-chain triglycerides (MCT, coconut oil C8–C10), Alpha-lipoic acid (thioctic acid, ALA), Cytoflavin (succinic acid, nicotinamide, riboflavin, inosine complex), L-arginine