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5 Ornithine Benefits (incl. Sleep) + Side Effects

Written by Jasmine Foster, BS (Biology), BEd | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Jasmine Foster, BS (Biology), BEd | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Ornithine

Ornithine is considered a non-essential amino acid that may improve recovery from exercise and injury. What is ornithine? How do we make it, and what does it do? Read on to learn more.

What Is Ornithine?

In the world of amino acids, ornithine is unusual. It doesn’t directly make proteins, and you don’t need to eat it in your diet, but it’s absolutely necessary for you to stay alive. How can that be?

Well, you don’t need to eat it because you can make your own. It’s important for life because it helps detoxify ammonia before it leaves the body. High levels of ammonia in the blood can cause all kinds of health problems, including cognitive defects and personality changes [1, 2, 3, 4].

L-Ornithine

Many commercial ornithine supplements specify that they contain L-ornithine. Amino acids are given an L or D designation depending on which potential mirror image form they take. The L indicates that the amino acid is in the “left-handed” form [5].

In living things, the L amino acids are far and away more common than the D amino acids [5].

Snapshot of Ornithine

Proponents:

  • Accelerates recovery times after exercise
  • Helps manage chronic liver disease
  • Improves wound (and especially burn) healing
  • May improve hangover recovery
  • Considered safe to supplement
  • Relatively easy to increase with diet choices

Skeptics:

  • High doses may cause nausea, diarrhea, and other side effects
  • Usefulness limited to periods of high stress
  • Expensive to supplement

How Does It Work?

The Urea Cycle

The urea cycle is one of your body’s waste management systems. It takes ammonia, a waste product of amino acid breakdown, and converts it to urea, which the kidneys can then excrete in urine [6].

Ornithine is an important gear in the machinery of the urea cycle. In the second step of the cycle, an enzyme called ornithine transcarbamylase takes ornithine and carbamoyl phosphate and converts them to citrulline and phosphate [6].

Thus, the theory behind ornithine supplements is that they may accelerate the urea cycle and improve the bodys waste management system.

Ornithine Decarboxylase

Besides the urea cycle, ornithine has a couple of other functions that are a little less understood. One of these is the production of polyamines: organic compounds that are highly concentrated in the brain. There’s a lot we don’t know about polyamines, but their levels decline with age [7].

Ornithine decarboxylase (ODC) is an enzyme that begins the process of building polyamines. Strangely, we can use ODC levels to detect certain types of cancer and bacteria [7, 8, 9, 10].

Formulations & Combinations

L-Ornithine HCl

Some ornithine supplements are sold as L-ornithine HCl. What’s the difference between these and other ornithine supplements? What is HCl?

In technical terms, L-ornithine hydrochloride (or L-ornithine HCl) is a chlorine salt of L-ornithine. That is, it’s a version of L-ornithine with a chlorine and a hydrogen atom attached. L-ornithine HCl has been the subject of multiple studies on physical fatigue and recovery from exercise, and it appears to be fairly effective for this purpose [11, 12, 13].

Ornithine Alpha-Ketoglutarate

Ornithine alpha-ketoglutarate, or OKG, is successfully used to improve burn healing and muscle protein building under stress [14, 15].

OKG is also a precursor for arginine (an amino acid) and nitric oxide (an antioxidant derived from arginine) [16].

Their combination is often supplemented to increase muscle gains and speed repair after intense exercise or injuries.

L-Ornithine and L-Arginine

L-ornithine and L-arginine are often sold as a combined supplement because L-arginine improves the absorption of ornithine into the cell. In theory, arginine should amplify the effects of ornithine supplements. Use caution, however: according to a cell study, arginine’s usefulness has a ceiling. Above a certain concentration, arginine reduced ornithine uptake [17].

Combined supplements of ornithine and arginine are, overall, probably more effective than ornithine alone.

L-Ornithine L-Aspartate (LOLA)

When L-ornithine and L-aspartate are given in combination, they are called LOLA. This combination is commonly used to manage the symptoms of hepatic encephalopathy, though it is probably only effective for chronic liver disease and not acute liver disease [18, 19, 20].

Potential Benefits (Possibly Effective)

Ornithine has produced positive results in multiple studies investigating athletic performance, but larger and more robust studies are required to confirm its effectiveness. Furthermore, because of the many common formulations and combinations of ornithine, it’s unclear which is best for any purpose. Talk to your doctor before starting a new supplement.

1) Athletic Performance

Ornithine supplements are relatively popular among athletes and bodybuilders. In a survey of a commercial gym on Long Island, 13.5% of clients said that they had tried ornithine, and 9% said they used it regularly [21].

Some evidence suggests that ornithine increases endurance and accelerates recovery after exercise. In two clinical studies, people taking ornithine recovered faster from exercise and reported feeling less fatigued. In one of these, ornithine appeared to increase people’s anaerobic (burst, sprint, or strength) performance [22, 13].

These results are controversial. Another study found no change at all in either performance or recovery in people taking ornithine [12].

Ornithine combination supplements may improve performance as well. L-ornithine L-aspartate (commonly called LOLA together) may accelerate recovery and increase mental sharpness during physical exercise. Ornithine and alpha-ketoglutarate (OAK) may protect muscle protein building in times of high stress, such as after a surgery [23, 14].

It’s important to note that all of these studies were very small, with fewer than 20 participants each. Larger studies will be required to fully understand how ornithine supplements affect performance.

Growth Hormone

Supplementing with human growth hormone increases muscle mass. It may not increase muscle strength, but it is still considered a doping agent and is banned in most sports leagues [24, 25].

Ornithine and arginine are believed to increase the body’s production of growth hormone. However, high doses are required to achieve this effect. Weightlifters experienced no increase in growth hormone after 2 g of ornithine per day; at a dose of 170 mg per kg of body weight (about 15.5 g per day for a 200 lb person), growth hormone increased significantly [26, 27, 28].

Other Potential Benefits with Insufficient Evidence

Ornithine has produced positive results in at least one study on each of the potential benefits in this section, but larger and more robust studies are required to confirm its effectiveness. Furthermore, because of the many common formulations and combinations of ornithine, it’s unclear which is best for any purpose. Talk to your doctor before starting a new supplement.

2) Sleep Quality

In a study of 52 stressed, but otherwise healthy Japanese adults, 400 mg of ornithine per day reduced fatigue and improved sleep quality. The participants reported that they felt less hostile or angry and more refreshed after a night of sleep [29].

Better yet, the study also found significantly reduced cortisol levels in the people taking ornithine supplements. Cortisol is a stress hormone; it can be used to measure stress, and it can also predict stress-related disease [29, 30, 31].

In mice, ornithine has been found to influence the sleep-wake cycle. Researchers are currently studying the possibilities of ornithine as a functional food to improve sleep quality [32, 33].

3) Chronic Liver Disease

The liver is the most important waste and toxin filtration system in the body, and when it fails, every other organ system is at risk – including the brain. Liver failure can impair cognition, behavior, and muscle control. This condition is called hepatic encephalopathy (HE), which literally means “liver brain disease” [34].

In cases of chronic liver disease, supplementing with L-ornithine L-aspartate (LOLA) has prevented episodes of HE. LOLA decreased blood ammonia and improves cognitive symptoms, even in people with severe end-stage disease [34].

Some researchers have suggested that people with chronic liver disease, even those who don’t have obvious cognitive symptoms, may benefit from supplementing with LOLA [35].

3) Wound Healing

Ornithine appears to accelerate wound healing. In mice, feeding ornithine after a cut increased the rate of healing and the strength of the new tissue [36].

This effect was especially dramatic in 42 burn victims given ornithine alpha-ketoglutarate (OKG). Even in severe cases where up to 95% of the body surface is burned, OKG accelerated the healing process and decreased protein breakdown [37, 38, 15].

When the body is healing a severe injury, it breaks down proteins to use for energy and to convert into new tissue. According to some authors, OKG may prevent that from happening, hence the decreased breakdown and accelerated healing [15, 37].

Do not attempt to self-administer OKG to treat any kind of wound. If you are severely burned or otherwise injured, seek medical attention immediately.

4) Hangover Recovery

In one study, 400 mg of ornithine after alcohol consumption decreased hangover symptoms and improved recovery. People who took ornithine reported feeling less fatigue, hostility, and confusion the morning after drinking [39].

This study had only eleven participants and only studied a 400 mg dose. Further studies will clarify the mechanism of this effect and whether larger or smaller doses are better for hangover relief [39].

Foods that Increase Ornithine

Ornithine is considered non-essential; we don’t need to eat it because our bodies can make it. However, some foods measurably increase ornithine in the blood. Surprisingly, the foods that appear to increase blood ornithine the most are grain proteins and watermelon [40, 15].

People who ate a diet high in grain proteins had significantly higher ornithine levels than those who ate mostly meat or dairy proteins. Meanwhile, people who drank large quantities of watermelon juice (more than a kilogram per day) experienced an 18% increase in blood ornithine [40, 15].

To increase your grain protein intake, choose whole grains with high protein content like quinoa and amaranth [41].

Side Effects & Safety

Ornithine is considered safe and well-tolerated for most people at lower doses. High doses of L-ornithine L-aspartate (LOLA) may cause nausea, cough, muscle cramps, or diarrhea. People with gyrate atrophy of the choroid and retina, a rare genetic eye disease, should avoid long-term ornithine supplementation, as it may cause retinal damage [35, 3].

Ornithine Transcarbamylase Deficiency

Ornithine transcarbamylase (OTC) is essential to the urea cycle. OTC deficiency, a rare genetic disorder, essentially breaks the cycle and causes ammonia to build up to dangerous levels [42, 43].

People with OTC deficiency cannot convert ornithine to citrulline in the urea cycle. They should avoid ornithine supplements, which could worsen their condition. They are also usually placed on low-protein diets because the amino acid arginine is converted to ornithine [42, 43].

Children

Ornithine ketoglutarate is sometimes used to maintain a normal growth rate in very sick, hospitalized children who need intravenous feeding. There is no particular reason to supplement ornithine in healthy children, and there are no studies on the potential risks [44].

Pregnancy

Some pregnant women may suffer from an ornithine deficiency. If there is no evidence of a deficiency, there appears to be no reason to supplement during pregnancy. There is a lack of information regarding taking ornithine while breastfeeding, so it is advised to avoid taking if you are breastfeeding [45].

Talk to your doctor if you are concerned about a potential ornithine deficiency.

Dosage

Commercial supplements recommend between 0.5 and 8 g per day and warn against taking more than 10 g per day.

Clinical studies have used a very wide range of doses for different purposes.

  • 400 mg per day improved sleep quality [29].
  • 400 mg in a single dose after drinking and before bed improved hangover recovery [39].
  • 2 g per day may or may not accelerate recovery after exercise [13, 46].
  • 100 mg per kg per day (6.8 g/day for a 150 lb person) increased anaerobic performance [22].
  • 170 mg per kg per day (11.6 g/day for a 150 lb person) increased growth hormone. This is above the recommended limit on most supplement labels [28].

Higher dosages increase the risk of side effects like nausea and diarrhea. Talk to your doctor before supplementing to avoid adverse events and unexpected interactions.

Limitations and Caveats

All human clinical trials of ornithine supplements suffer from very low sample sizes. Few human trials have more than 20 participants; as a result, their conclusions must all be taken with a grain of salt.

One consequence of the small size of these studies is that no single study could investigate a range of doses. Studies showing no benefit may not have used a large enough dose, and different doses may have different benefits and drawbacks. Hopefully, future studies will be large and powerful enough to figure out these details.

Finally, some studies supporting claims of benefits to athletic performance were funded and supplied by the manufacturers of ornithine supplements.

Takeaway

Ornithine is a “non-essential” amino acid that the body can make on its own. The body may benefit from additional amounts in periods of high stress – such as after strenuous exercise, due to cuts and wounds, during pregnancy, or due to chronic liver disease.

Ornithine is part of the urea cycle, which converts ammonia (a waste molecule) into urea so the kidneys can remove it. It can be taken alone or as OKG or LOLA; supplements may also combine it with arginine. Ornithine is considered safe, though large doses may cause cough, nausea, diarrhea, or muscle cramps.

Eating more grain proteins and watermelon may boost ornithine without the need for supplements.

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About the Author

Jasmine Foster

Jasmine Foster

BS (Biology), BEd
Jasmine received her BS from McGill University and her BEd from Vancouver Island University.
Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

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