L-Ornithine - An Overview
L-ornithine is a common amino acid that naturally occurs in the liver. It can be taken as a nootropic supplement for:25Morris SM Jr. Regulation of enzymes of the urea cycle and arginine metabolism, Annu Rev Nutr. 2002
- Stress and anxiety
- Physical performance
L-ornithine is a non-essential amino acid. Although you can get L-ornithine from some foods, the amount is usually small.
Since ancient times, corbicula, a clam rich in this compound, has been eaten for liver health.
This nootropic is generally considered useful for lowering anxiety and increasing energy holistically, especially under stressful situations.
Some users also report brighter moods and more energy. It may be a useful supplement for athletes as well.
L-ornithine works primarily by modulating the GABA system, lowering stress hormones, buffering ammonia toxicity, and disposing of excess nitrogen.
What Does L-Ornithine Do?
Research shows that L-Ornithine can attenuate the stress response sent from the hypothalamus.
It can modulate the GABA system, which is responsible for relaxation and keeping your central nervous system from getting overloaded.1Kurata K, et al. L-ornithine attenuates corticotropin-releasing factor-induced stress responses acting at GABAA receptors in neonatal chicks, Neuroscience. 2011
This means that it may lower your automatic physical reaction to overstimulation, and help you keep calm and steady in trying situations.2Kurata K, et al. L-ornithine attenuates corticotropin-releasing factor-induced stress responses acting at GABAA receptors in neonatal chicks, Neuroscience. 2011
One study on healthy workers showed that L-ornithine has a positive effect on stress and sleep.
The participants that took this nootropic had lower cortisol levels and better self reported scores on stress than the placebo group.
The researchers concluded that L-ornithine might be beneficial for people who have stressful schedules.3Mika Miyake. Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers, Nutr J. 2014
L-ornithine can lower anxiety-related behavior in both animals and humans according to multiple trials.
Multiple studies on human volunteers showed that it lowered overall anxiety scores when taken daily for multiple weeks.
Although the studies were fairly small and short-term, the groups that took L-ornithine saw an across-the-board improvement on most measures of anxiety.4Deborah Armborst, et al. Impact of a Specific Amino Acid Composition with Micronutrients on Well-Being in Subjects with Chronic Psychological Stress and Exhaustion Conditions: A Pilot Study, Nutrients. 2018 5Mika Miyake. Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers, Nutr J. 2014
Orally administrated L-ornithine also reduced anxiety responses in rats that were subjected to maze tests.6Kurata K, et al. Orally administered L-ornithine elevates brain L-ornithine levels and has an anxiolytic-like effect in mice, Nutr Neurosci. 2011
Although more research is needed, initial results suggest that L-ornithine could be a potent anxiolytic.
L-ornithine may also improve sleep patterns.
In an 8 week randomised, double-blind and placebo-controlled trial with 52 healthy adults, it seemed to have some positive effects on sleep.
L-Ornithine outperformed placebo in terms of time to fall asleep, maintenance of sleep, and feeling refreshed.7Mika Miyake. Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers, Nutr J. 2014
Another study showed that L-ornithine can increase the amount of non-REM sleep without reducing the overall quality of non-REM sleep.9Ken OMORI, et al. Promotion of non–rapid eye movement sleep in mice after oral administration of ornithine, Sleep And Biological Rhythms. 2011
In a rat study, L-ornithine released growth hormones which are secreted after the onset of sleep. Researchers believe here is a correlation between night-time growth hormone release and sleep satisfaction.
Although there are no human studies on this, it could indicate that L-ornithine could increase feelings of refreshment through this action.10Jeevanandam M, et al. Ornithine-alpha-ketoglutarate (OKG) supplementation is more effective than its component salts in traumatized rats, J Nutr. 1996
There is some evidence that L-ornithine may increase melatonin production, which is a critical hormone for sleep-regulation.11Paredes SD, et al. Melatonin and tryptophan affect the activity-rest rhythm, core and peripheral temperatures, and interleukin levels in the ringdove: changes with age, J Gerontol A Biol Sci Med Sci. 2009
It also may improve sleep quality for people who have consumed alcohol.12Takeshi Kokubo, et al. L－ornithine－L－aspartate Improves Alcohol－derived Fatigue Feeling in Flushers―A Questionnaire Study, 薬理と治療. 2012
Energy and Fatigue
L-ornithine may increase physical stamina and reduce fatigue. Some users report more energy in the gym while taking this nootropic.
L-ornithine can increase the body’s ability to buffer ammonia, both during and after exercise. By reducing ammonia, it could provide more endurance during physical activities.13Demura S, et al. The effect of L-ornithine hydrochloride ingestion on performance during incremental exhaustive ergometer bicycle exercise and ammonia metabolism during and after exercise, Eur J Clin Nutr. 2010 14Demura S, et al. Effect of L-ornithine hydrochloride ingestion on intermittent maximal anaerobic cycle ergometer performance and fatigue recovery after exercise, Eur J Appl Physiol. 2011
Exercise-induced hyperammonemia (i.e. what makes your muscles feel sore during exercise) may also destabilize brain function.
This may negatively impact fatigue and overall mental and physical performance during intense exertion.15Wilkinson DJ. Ammonia metabolism, the brain and fatigue; revisiting the link, Prog Neurobiol. 2010
One study found that oral L-ornithine promoted fat metabolism and lowered blood ammonia level in healthy athletes.
L-ornithine significantly lowered the subjective feelings of fatigue compared to placebo.
These results suggest that L-ornithine has an antifatigue effect by increasing the efficiency of energy consumption and promoting the excretion of ammonia.16Sugino T, et al. NL-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism, Nutr Res. 2008
By lowering anxiety and stress, L-ornithine can also have a positive effect on overall mood.
Multiple human studies showed this nootropic was able to improve feelings of well-being.
L-Ornithine can contribute to better overall mood and quality of life, especially in people under stressful circumstances.17Mika Miyake. Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers, Nutr J. 2014 18Deborah Armborst, et al. Impact of a Specific Amino Acid Composition with Micronutrients on Well-Being in Subjects with Chronic Psychological Stress and Exhaustion Conditions: A Pilot Study, Nutrients. 2018
How L-Ornithine Works In The Brain
Orally administered L-ornithine is quickly metabolized in the intestines and then delivered to various tissues, such as the liver, kidney and muscle.
In the liver, L-ornithine plays a central role in the urea cycle, which converts ammonia to urea.19Vaubourdolle M, et al. Fate of enterally administered ornithine in healthy animals: interactions with alpha-ketoglutarate, Nutrition. 1989
This function can enhance detoxification of ammonia in the liver and potentially improve mental and physical performance.
It may also protect the liver from long-term damage.20Skowrońska M, et al. Alterations of blood brain barrier function in hyperammonemia: an overview, Neurotox Res. 2012
It can also modulate the GABA system, which is necessary for regulating stress.
By acting on GABA receptors, L-ornithine can reduce overstimulation and improve overall feelings of anxiety and mood.22Anuradha H. Euphorbia hirta reverses chronic stress-induced anxiety and mediates its action through the GABA(A) receptor benzodiazepine receptor-Cl(-) channel complex, J Neural Transm (Vienna). 2008
L-ornithine also lowers levels of cortisol in the blood. Cortisol is a major stress hormone.
So by modulating this system, L-ornithine can prevent negative anxiety responses.23Kurata K, et al. Orally administered L-ornithine reduces restraint stress-induced activation of the hypothalamic-pituitary-adrenal axis in mice, Neurosci Lett. 2012
Some preliminary evidence also suggests that L-ornithine may be able to modulate the serotonin and dopamine systems (in animals, at least).
These are major pathways responsible for mood and emotion, which may indicate how L-ornithine can affect positive feelings.24Gruss M, Braun K. Distinct activation of monoaminergic pathways in chick brain in relation to auditory imprinting and stressful situations: a microdialysis study, Neuroscience. 1997
L-Ornithine Potential Side Effects
L-ornithine is considered safe and non-toxic, with virtually no potential for overdose.
It is a naturally occurring compound found in the body. There are no known side-effects when taken in the proper doses.
There are no known drug interactions.
We strive to bring you the most up to date, research-based information about L-Ornithine and other nootropics.
Something we missed? Do you use L-Ornithine? Share your thoughts and experiences in the comments below.
About the author:
Erik Levi is a co-founder of HolisticNootropics.com and a certified holistic nutritional therapy practitioner.
As an NTP Erik takes a nutrition first approach to health. He has worked with many different people to help them use nutrition to optimize their quality of life.
Erik believes that mental health is a physiological process and cognitive enhancement is not something that can be achieved by just taking some pills with good Amazon reviews.
Instead, true cognitive enhancement comes with the right balance of nutrients, movement, and gratitude. Erik continues to stay up to date with the most current nootropic and holistic health research and promises to deliver the best solutions possible.
You can check out his personal health blog/podcast/YouTube Channel all under the name Holistic A-Hole.