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Ornithine

Ornithine is one of the three amino acids involved in the Urea cycle, alongside L-Arginine and L-Citrulline; this amino acids appears to reduce elevated ammonia levels when supplemented, and preliminary evidence suggests an ergogenic role due to this.

Our evidence-based analysis on ornithine features 65 unique references to scientific papers.

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Summary of Ornithine

Primary information, health benefits, side effects, usage, and other important details

L-Ornithine is a nonprotein amino acid (not used to create proteins) that is an intermediate of the urea cycle, and provision of ornithine to a cell is actually the rate limiting step of the cycle. Ornithine binds with a molecule known as carbamoyl phosphate which requires ammonia to be produced and then is converted into L-Citrulline giving off urea as a byproduct. Due to this, the conversion is one that reduces ammonia concentrations in the blood and concomitantly increases urea.

L-Ornithine is thought to be important for conditions that are characterized by an excess level of ammonia, and this is mainly focused on either hepatic encephalopathy (clinical liver condition) or prolonged cardiovascular exercise. A reduction in serum ammonia has been repeatedly found in persons with hepatic encephalopathy (most studies use infusions, although it appears to apply to high dose oral supplements as well) while there are only two studies assessing exercise; the one that was better suited to assess the influence of ammonia (using prolonged exercise rather than acute exercise) did find an anti-fatigue effect.

Furthermore, reductions in self-reported fatigue have been noted in persons with hepatic encephalopathy and in persons subject to a hangover (the process of getting drunk off of alcohol will increase serum ammonia) when ornithine is taken before drinking, but only in persons sensitive to alcohol perhaps.

There is currently one study using ornithine paired with arginine that noted improvements in lean mass and power output in weightlifters, but this is an old study that has not been replicated and its practical relevance is uncertain.

Finally, the increases in growth hormone seen with ornithine are similar to those seen with arginine. Technically they exist, but as they are very short lived and the body seems to compensate the overall increaes in whole-day growth hormone are not significant. Since the main properties of growth hormone being concerned with (increased lean mass gain and fat loss) are more related to day-long exposure rather than short-bursts, it is unlikely that ornithine has a role here.

In the end, ornithine looks somewhat promising for reducing ammonia concentrations in the blood and thus enhancing performance of prolonged exercise (45 minutes or more) which is in part due to it being elevated in the blood for a few hours after ingestion despite exercise.

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How to Take

Medical Disclaimer

Recommended dosage, active amounts, other details

Ornithine supplementation (as hydrochloride) is taken in the range of 2-6g daily. Most studies use a dose in this range, but despite serum levels being somewhat dose dependent there is a chance of intestinal distress at doses above 10g.

Most studies use Ornithine hydrochloride (Ornithine HCl) which appears to be effective. Ornithine HCl is 78% Ornithine by weight, and so for the 2-6g range an equivalent dose for L-Ornithine L-Aspartate (50% Ornithine) would be 3.12-9.36g and an equivalent dose for L-Ornithine α-ketoglutarate (47% Ornithine) would be 3.3-10g. These two forms are theoretically more effective, but lack sufficient comparative testing.

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Human Effect Matrix

Unlocked for Examine members

The Human Effect Matrix summarizes human studies to tell you what effects Ornithine has on your body, how much evidence there is, and how strong these effects are.

Full details are available to Examine members.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-b - High See all 3 studies
For the most part there is no significant effect, although one trial did note that after exercise during a recovery period ornithine had a higher heart rate. The reason for this is not known
grade-c
Minor
- See 2 studies
Although supplementation of Ornithine is recommended to reduce ammonia (which it appears to do in both models of hepatic encephalopathy and prolonged physical exercise) at least one study noted that for short term strenuous exercise ornithine caused an increase in ammonia
grade-c
Minor
- See study
Increases have been noted with intravenous ornithine (not in human trials table) while decreases have been noted following treatment of hangovers. The most practical study of using ornithine as a preworkout supplement failed to find any effect
grade-c Minor Very High See 2 studies
A reduction in fatigue has been noted for both prolonged exercise, hepatic pathology, and for hangovers; all situations characterized by excessive ammonia concentrations in the blood.
grade-c Minor - See study
The increase in sleep quality was secondary to reducing the adverse effects of excessive drinking, and was measured by self-report
grade-c Minor Moderate See 2 studies
Mixed effects, but it appears that when ammonia is decreased that urea is also increased but if ammonia is unchanged whatever reason for this also means that urea is unchanged.
grade-c - - See study
Performance during short term cardiovascular exercise (assessed by time to exhaustion) does not appear to be significantly affected.
grade-c - - See study
No significant interactions with blood pressure
grade-c - - See study
Oxygen uptake during exercise does not appear to be significantly altered
grade-c - - See study
No significant influence on the amount of work that can be conducted on a cycle ergometer during short-term testing

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Things to Note

Is a Form Of

Primary Function:

Also Known As

L-Ornithine

Goes Well With

  • Anionic salts such as Alpha-Ketoglutarate

  • Arginine is known to cause diarrhea at doses of 10g or higher, and since Ornithine shares the same intestinal transporters (diarrhea occurs when the transporter gets saturated) it is possible that supplemental ornithine can reduce the amount of arginine requires to induce diarrhea

  • Ornithine itself in high doses can induce diarrhea (10-20g), but is likely a lesser concern than is arginine

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Click here to see all 65 references.