L-Ornithine | Supplementopedia

Overview

L‑Ornithine is a non‑essential, α‑amino acid that participates in the urea cycle, the primary pathway for detoxifying ammonia in mammals. While it can be synthesized from L‑arginine and other amino acids, supplemental L‑ornithine is commonly taken to support nitrogen balance, support recovery after intense exercise, and aid in hepatic detoxification.

Benefits

Exercise performance & recovery: Clinical trials show that 2–6 g of L‑ornithine taken before or after training reduces perceived fatigue and improves nitrogen balance, facilitating muscle repair (Kawamura et al., 2021).
Cognitive function under stress: Small‑scale human studies demonstrate improved mental clarity and reduced subjective stress when 3 g/day is taken for 4 weeks, likely mediated by reduced ammonia‑induced neurotoxicity.
Liver health & urea cycle support: In patients with mild hepatic insufficiency, 5 g/day lowered serum ammonia and improved liver‑function test scores (Sanchez‑Mendoza et al., 2020).
Immune modulation: Ornithine‐derived polyamines (e.g., spermidine) enhance lymphocyte proliferation, suggesting a modest immune‑support role in older adults.
Overall, benefits are modest and most robust when combined with a balanced diet and adequate protein intake.

How It Works

Process: L‑Ornithine acts principally as a substrate for the urea cycle, where it is converted to citrulline by ornithine transcarbamylase, ultimately producing urea and freeing ammonia for excretion. This detoxification lowers circulating ammonia, a neurotoxic metabolite.
Pathway: Ornithine also feeds the polyamine pathway: ornithine decarboxylase transforms it into putrescine, which is further converted to spermidine and spermine. These polyamines regulate cell proliferation, DNA stabilization, and autophagy, contributing to tissue repair and immune function.
Growth Hormone: Additionally, ornithine stimulates growth hormone (GH) secretion via hypothalamic‑pituitary signaling, which may partially explain observed improvements in muscle recovery and body composition.
The combined effects on nitrogen clearance, polyamine synthesis, and GH modulation underlie the reported physiological benefits.

Dosage

General health / liver support: 2–5 g/day, split into two doses (morning and evening) taken with meals.
Athletic performance / recovery: 3–6 g taken 30 min before exercise or immediately post‑workout; a second 2 g dose before bedtime may improve overnight recovery.
Stress‑related cognition: 3 g/day, divided into morning and early‑afternoon doses to sustain steady plasma levels.
Special populations: Pregnant or lactating women should limit intake to ≤3 g/day and only under medical supervision.
Cycling: Some protocols suggest 4–8 weeks on, 2 weeks off to avoid potential adaptive down‑regulation of endogenous ornithine synthesis, although evidence for a necessary cycle is limited.

Safety & Side Effects

L‑Ornithine is generally well‑tolerated; reported side effects are mild and include gastrointestinal discomfort (bloating, nausea) at doses >10 g/day.
Contraindications:
- Severe hepatic dysfunction (where ammonia metabolism is compromised)
- Hyperammonemia
- Known ornithine transcarbamylase deficiency
Potential drug interactions:
- Concurrent high‑dose arginine may amplify nitric‑oxide–mediated vasodilation, affecting antihypertensive therapy.
- Concurrent use with diuretics may exacerbate electrolyte loss.
Pregnant, lactating women, and children under 12 should avoid high‑dose supplementation unless directed by a clinician.
Long‑term safety data (>1 year) are limited; routine monitoring of liver enzymes and plasma ammonia is advisable for high‑dose or chronic users.

Chemistry

L‑Ornithine (L‑2,5‑diamino‑pentanoic acid) has the molecular formula C₅H₁₂N₂O₂ and a molecular weight of 132.16 g·mol⁻¹.
Its IUPAC name is (2S)-2,5‑Diaminopentanoic acid.
The molecule features a central α‑carboxyl group, an α‑amino group, and a side‑chain ε‑amino group, giving it a basic, water-soluble character (pKa ≈ 9.5 for the side‑chain amine).
It exists as a zwitterion at physiological pH, allowing efficient transport across cellular membranes via cationic amino‑acid transporters (e.g., CAT2).
The presence of two amino groups makes it a key substrate for transamination and decarboxylation reactions within the urea and polyamine pathways.

Sources & Quality

Commercial L‑ornithine is primarily derived from fermentation of Corynebacterium or Escherichia coli strains engineered to overproduce the amino acid, providing a high-purity, vegan‑compatible product.
Small‑scale production also uses chemical synthesis via the Strecker or Michael addition routes, though these may generate racemic mixtures requiring chiral separation for the L‑isomer.
Natural dietary sources contain only modest amounts (e.g., meat, fish, dairy, and certain legumes).
For supplements, manufacturers should verify:
- (1) ≥98 % L‑ornithine purity
- (2) absence of heavy‑metal or microbial contaminants (USP/ISO 17025 testing)
- (3) compliance with Good Manufacturing Practices (GMP).
Products labeled as “fermented” typically have fewer residual solvents compared with chemically synthesized alternatives.