L-Ornithine

• Ammonia detoxification
• Liver health support
• Exercise recovery

• Wound healing
• Immune function
• Growth hormone support
• Stress reduction
• Sleep quality improvement

L-Ornithine functions through several key mechanisms in the body: 1) Urea Cycle: L-Ornithine is a central component of the urea cycle, which is the primary pathway for ammonia detoxification in the body. In this cycle, L-ornithine combines with carbamoyl phosphate (derived from ammonia) to form L-citrulline, which is eventually converted to L-arginine and then back to L-ornithine, completing the cycle. This process converts toxic ammonia into urea, which can be safely excreted by the kidneys. 2) Polyamine Synthesis: L-Ornithine serves as a precursor for the synthesis of polyamines (putrescine, spermidine, and spermine) via the enzyme ornithine decarboxylase.

Polyamines are essential for cell growth, proliferation, and DNA synthesis, playing important roles in tissue repair and immune function. 3) Proline and Glutamate Synthesis: L-Ornithine can be converted to proline, an amino acid crucial for collagen synthesis and wound healing. It can also be metabolized to glutamate, which serves as a neurotransmitter and precursor for glutamine synthesis. 4) Growth Hormone Secretion: Some research suggests that L-ornithine supplementation may stimulate the release of growth hormone, particularly when combined with exercise.

This effect may contribute to its potential benefits for muscle recovery and growth. 5) Ammonia Buffering in Exercise: During intense exercise, ammonia accumulates in muscles and blood, contributing to fatigue. L-Ornithine supplementation may help buffer this ammonia, potentially delaying fatigue and improving exercise performance. 6) Hepatoprotective Effects: When administered as L-ornithine L-aspartate (LOLA), it enhances ammonia detoxification in both periportal and perivenous hepatocytes through complementary mechanisms.

In periportal cells, ornithine stimulates urea synthesis, while in perivenous cells, both ornithine and aspartate enhance glutamine synthesis, effectively removing ammonia from circulation. 7) Stress Reduction: L-Ornithine may reduce cortisol levels and subjective feelings of stress and fatigue, possibly through its role in ammonia detoxification and/or through effects on neurotransmitter systems. 8) Wound Healing and Tissue Repair: As L-ornithine alpha-ketoglutarate (OKG), it may promote protein synthesis and inhibit protein catabolism, supporting wound healing and recovery from trauma or surgery. 9) Immune Function: Through its role in polyamine synthesis and potential anti-inflammatory effects, L-ornithine may support immune function, particularly in states of stress or trauma.

10) Sleep Quality: Some evidence suggests that L-ornithine supplementation may improve sleep quality and reduce feelings of fatigue, possibly through its effects on stress hormones and/or neurotransmitter systems.

The effective dosage range for L-Ornithine varies based on the form used and the intended purpose. For general health support, doses typically range from 2-6 grams per day. For specific therapeutic applications, particularly when using L-ornithine L-aspartate (LOLA) for liver conditions, higher doses may be used under medical supervision.

L-Ornithine is absorbed in the small intestine through both passive diffusion and active transport mechanisms, primarily via the b0,+ amino acid transport system. The absorption rate is generally good, with peak plasma concentrations typically occurring 1-2 hours after oral ingestion. However, as with many amino acids, absorption can be affected by the presence of other amino acids that compete for the same transporters. The bioavailability of free-form L-ornithine is estimated to be approximately 40-60% when taken orally.

L-Ornithine L-aspartate (LOLA) may have enhanced bioavailability compared to free-form L-ornithine, particularly for liver-targeted effects, as both components contribute to ammonia detoxification through complementary mechanisms. L-Ornithine alpha-ketoglutarate (OKG) may also have unique bioavailability characteristics, with the alpha-ketoglutarate component potentially enhancing the metabolic effects of ornithine.

Taking on an empty stomach: Consuming L-ornithine on an empty stomach may improve absorption by reducing competition with other amino acids from dietary protein., Specialized forms: L-Ornithine L-aspartate (LOLA) and L-Ornithine alpha-ketoglutarate (OKG) may offer enhanced bioavailability and targeted effects compared to free-form L-ornithine., Divided dosing: For larger doses (>5g), dividing the total daily dose into 2-3 smaller doses throughout the day may improve overall absorption and utilization., Combining with carbohydrates: Some evidence suggests that consuming L-ornithine with carbohydrates may enhance its uptake into tissues, possibly through insulin-mediated mechanisms., Avoiding high-protein meals: Taking L-ornithine away from high-protein meals may reduce competition for absorption with other amino acids.

For exercise performance and recovery, L-ornithine is typically taken either 30-60 minutes before exercise or before bedtime. When used for liver support, particularly as LOLA, divided doses throughout the day are often recommended to maintain more consistent blood levels. For stress reduction and sleep improvement, taking L-ornithine approximately 30-60 minutes before bedtime appears to be most effective. When using L-ornithine for growth hormone stimulation, taking it on an empty stomach, either before exercise or before sleep, may be most effective.

For general health purposes, L-ornithine can be taken with or without food, though absorption may be slightly better on an empty stomach. If gastrointestinal discomfort occurs, taking L-ornithine with a small amount of food may help mitigate these effects without significantly compromising absorption.

• Gastrointestinal discomfort (mild stomach pain, nausea, or diarrhea), particularly at higher doses
• Mild diarrhea or soft stools
• Nausea or stomach discomfort
• Headaches (uncommon)
• Dizziness (rare)
• Fatigue or weakness (rare)
• Sleep disturbances (rare, typically at high doses)

• Individuals with severe liver disease should use L-ornithine only under medical supervision, particularly when not in the form of L-ornithine L-aspartate (LOLA)
• Individuals with severe kidney disease should use caution, as impaired kidney function may affect ornithine metabolism and excretion
• Pregnant or breastfeeding women (insufficient safety data)
• Individuals with bipolar disorder or schizophrenia should use caution, as amino acids that affect neurotransmitter systems may potentially influence mood disorders
• Individuals with phenylketonuria should be aware that some L-ornithine supplements may contain phenylalanine as part of the formulation
• Individuals with herpes simplex infections (theoretical concern that increased arginine levels from ornithine metabolism might promote viral replication)

• Medications for liver disease: May have additive or interactive effects with L-ornithine, particularly LOLA
• Growth hormone medications: Potential additive effects with L-ornithine’s possible growth hormone-stimulating properties
• Immunosuppressants: Theoretical interaction due to L-ornithine’s potential effects on immune function
• Medications metabolized by the liver: High doses of L-ornithine may potentially affect liver enzyme activity, though clinical significance is unclear
• Ammonia-lowering medications: May have additive effects with L-ornithine’s ammonia-lowering properties

No established upper limit by major regulatory bodies. Clinical studies have used doses up to 18 grams per day of L-ornithine L-aspartate (LOLA) with minimal adverse effects. For free-form L-ornithine, doses up to 10 grams daily have been used in research with generally good tolerability, though gastrointestinal side effects become more common at higher doses. L-Ornithine alpha-ketoglutarate (OKG) has been used at doses up to 30 grams daily in clinical settings for severe trauma or burns, but such high doses should only be used under medical supervision.

For most individuals, staying within the 2-6 gram per day range for free-form L-ornithine minimizes the risk of side effects while potentially providing benefits. Long-term safety studies beyond several months are limited, though L-ornithine is an endogenous compound naturally produced in the body, suggesting good long-term safety profile when used appropriately.

In the United States, L-Ornithine is classified as a dietary supplement ingredient under the Dietary Supplement Health and Education Act (DSHEA) of 1994. It is generally recognized as safe (GRAS) when used as directed. As a supplement, manufacturers cannot make specific disease claims without FDA approval, but can make general structure/function claims related to exercise recovery, liver health, and ammonia metabolism. The FDA has not established a recommended daily allowance (RDA) or tolerable upper intake level (UL) for L-ornithine.

L-Ornithine L-aspartate (LOLA) is not approved as a drug by the FDA for any specific indication, though it is widely used in many other countries for liver disorders. It is available in the US only as a dietary supplement.

The European Food Safety Authority (EFSA) has evaluated several health claims for L-ornithine but has not approved any specific health claims due to insufficient evidence. L-ornithine is regulated as a food supplement under Directive 2002/46/EC. In several European countries, L-ornithine L-aspartate (LOLA) is approved as a medication for the treatment of hepatic encephalopathy and other liver disorders characterized by hyperammonemia.

It is available by prescription in countries such as Germany, Italy, and Spain under various brand names.

Health Canada permits L-ornithine as a Natural Health Product (NHP) ingredient. It is listed in the Natural Health Products Ingredients Database (NHPID) with both medicinal and non-medicinal roles. Health Canada has approved certain claims related to L-ornithine’s role in ammonia metabolism and liver function when specific conditions are met. L-Ornithine L-aspartate (LOLA) is available as a prescription medication for liver disorders in Canada.

The Therapeutic Goods Administration (TGA) of Australia regulates L-ornithine as a listed complementary medicine ingredient. It can be used in listed medicines with appropriate evidence for its safety and quality. L-Ornithine L-aspartate (LOLA) is registered as a prescription medication for the treatment of hepatic encephalopathy and related liver disorders in Australia.

Regulations regarding L-ornithine supplementation vary significantly by country. In Japan, L-ornithine is recognized under the Foods for Specified Health Uses (FOSHU) system for certain applications related to fatigue reduction. In Russia and several Eastern European countries, both L-ornithine and its specialized forms (LOLA, OKG) are often classified as metabolic medications rather than supplements. L-Ornithine L-aspartate (LOLA) is approved as a prescription medication for liver disorders in many countries worldwide, including most of Europe, parts of Asia, and Latin America.

It is marketed under various brand names, including Hepa-Merz, Hepamerz, and Orniliv. Some countries have established maximum daily doses for supplement use, typically ranging from 2-6 grams per day for free-form L-ornithine.

Free-form L-ornithine is available as an over-the-counter supplement in most countries without prescription. L-Ornithine L-aspartate (LOLA) requires a prescription in many countries where

it is approved as a medication for liver disorders, including most European countries, Canada, and Australia. In the United States, LOLA is only available as a dietary supplement, not as a prescription medication. L-Ornithine alpha-ketoglutarate (OKG) is typically available as a dietary supplement without prescription, though in some countries

it may be used in clinical settings under medical supervision for specific conditions such as severe trauma or malnutrition.

L-Ornithine supplements typically range from $0.15 to $0.50 per gram for L-ornithine hydrochloride powder, and $0.25 to $0.70 per gram for capsule or tablet forms. Specialized forms such as L-ornithine L-aspartate (LOLA) and L-ornithine alpha-ketoglutarate (OKG) are generally more expensive, ranging from $0.30 to $1.00 per gram. For a typical monthly supply at a dosage of 3 grams per day, consumers can expect to pay approximately $15-$45 for basic L-ornithine supplements, $25-$75 for LOLA, and $30-$90 for OKG.

Prescription-grade LOLA, where available, may be significantly more expensive without insurance coverage.

When compared to other amino acid supplements, L-ornithine offers moderate value, particularly in its basic hydrochloride form. It is generally more expensive per gram than common amino acids like glycine or glutamine but less expensive than some specialized amino acids or peptides. For liver support, L-ornithine L-aspartate (LOLA) offers good value compared to some prescription medications for hepatic encephalopathy, though its effectiveness may vary depending on the specific condition and severity. For exercise performance and recovery, basic L-ornithine provides moderate value compared to other supplements with similar claims, such as branched-chain amino acids (BCAAs) or creatine.

However, the evidence for its benefits in this context is less robust than for some alternatives. For stress reduction and sleep improvement, lower doses of L-ornithine (400-800mg) may offer good value compared to many other sleep and stress supplements, though individual responses vary significantly.

Purchasing L-ornithine hydrochloride powder in bulk (250g-1kg) can significantly reduce costs, often bringing the price down to $0.10-$0.20 per gram.

This approach is most economical for those requiring higher doses or long-term supplementation.

However , proper measurement tools (such as a milligram scale) and storage containers are necessary

when purchasing bulk powder. Specialized forms like LOLA and OKG are less commonly available in bulk formats for individual consumers, though healthcare institutions may have access to bulk purchasing options.

Free-form L-ornithine supplements are typically not covered by conventional health insurance plans. In countries where L-ornithine L-aspartate (LOLA) is approved as a prescription medication for liver disorders,

it may be covered by health insurance

when prescribed for approved indications. Coverage varies by insurance provider, specific plan, and country. Some Health Savings Accounts (HSAs) or Flexible Spending Accounts (FSAs) may cover L-ornithine supplements with a physician’s recommendation, though policies vary widely.

Pure L-Ornithine hydrochloride (HCl) typically has a shelf life of 2-3 years when stored properly. L-Ornithine in capsule or tablet form generally has a shelf life of 2-3 years, depending on the formulation and presence of other ingredients. L-Ornithine L-aspartate (LOLA) and L-Ornithine alpha-ketoglutarate (OKG) may have slightly shorter shelf lives (1.5-2.5 years) due to the potential for the additional components to affect stability over time.

Store in a cool, dry place away from direct sunlight, Optimal temperature range: 15-25°C (59-77°F), Keep container tightly closed to protect from moisture, Refrigeration is not necessary but may extend shelf life, For powder forms, use the provided scoop or a clean, dry utensil to prevent moisture introduction, L-Ornithine hydrochloride is hygroscopic (attracts moisture) and should be stored with extra care to prevent clumping, Specialized forms (LOLA, OKG) may have specific storage requirements; follow manufacturer recommendations

Exposure to high humidity (can cause clumping and degradation of powder forms), Prolonged exposure to high temperatures (>30°C/86°F), Direct sunlight or UV radiation, Oxidation (particularly in solution), Microbial contamination if exposed to moisture, Extreme pH conditions (highly acidic or alkaline environments), For specialized forms (LOLA, OKG), the additional components may be more susceptible to degradation under certain conditions

L-Ornithine hydrochloride is generally stable in aqueous solution at slightly acidic to neutral pH for short periods (1-2 weeks) when refrigerated. Stability decreases in strongly alkaline conditions. For maximum stability in solution, a pH range of 5.5-7.0 is optimal. Solutions should be stored in the refrigerator (2-8°C) in a tightly sealed container.

L-Ornithine L-aspartate (LOLA) solutions are typically more stable at slightly acidic pH (5.0-6.5). L-Ornithine alpha-ketoglutarate (OKG) solutions may be less stable due to the potential for the alpha-ketoglutarate component to degrade over time. Pre-mixed solutions should ideally be consumed within 24-48 hours for optimal potency. When mixed in protein shakes or sports drinks, L-ornithine remains stable for several hours at room temperature but should be consumed within the same day for best results.

Natural Sources

Synthetic Production Methods

Quality Indicators

Sustainability Considerations

Unlike many other nutritional compounds, L-Ornithine does not have a significant documented history of traditional medicinal use as an isolated compound. As a non-proteinogenic amino acid that is primarily involved in metabolic processes within the body,

it was not recognized or isolated in traditional medicine systems.

However , foods rich in protein, which provide the precursors for ornithine synthesis (particularly arginine), have been valued in various cultures for their strength-giving and healing properties. Traditional high-protein diets, particularly those rich in animal products, would have naturally supported the body’s ornithine metabolism, though

this connection was not understood until modern biochemistry emerged.

L-Ornithine was first isolated in 1877 by the German chemist Wilhelm Kühne from animal extracts. Its name is derived from the Latin ‘ornis’ meaning ‘bird,’ as it was first isolated from the urine of birds. The structure of ornithine was established in the early 20th century, but its biological significance remained unclear until the discovery of the urea cycle by Hans Krebs and Kurt Henseleit in 1932. Their groundbreaking work identified ornithine as a key intermediate in the urea cycle, the primary pathway for ammonia detoxification in mammals.

In the 1950s and 1960s, research further elucidated ornithine’s role in various metabolic pathways, including polyamine synthesis and its relationship to arginine metabolism. The development of L-ornithine L-aspartate (LOLA) as a therapeutic agent for liver disease began in the 1960s, with early clinical studies in Germany demonstrating its efficacy for reducing ammonia levels in patients with hepatic encephalopathy. L-Ornithine alpha-ketoglutarate (OKG) was developed in the 1980s, primarily for its potential benefits in wound healing, trauma recovery, and protein metabolism.

Initially, L-ornithine was primarily of interest to biochemists studying metabolic pathways rather than being recognized for therapeutic potential. The first clinical applications emerged in the 1960s and 1970s, focusing on L-ornithine L-aspartate (LOLA) for the treatment of hepatic encephalopathy and other liver disorders characterized by hyperammonemia. By the 1980s, L-ornithine alpha-ketoglutarate (OKG) was being investigated for its potential benefits in wound healing, recovery from trauma or surgery, and treatment of malnutrition. This application was based on OKG’s ability to stimulate protein synthesis and reduce protein catabolism.

The late 1980s and 1990s saw increased interest in L-ornithine for sports performance, with claims related to growth hormone stimulation, exercise recovery, and ammonia buffering during intense exercise. This period also saw the beginning of research into L-ornithine’s potential benefits for stress reduction and sleep quality. In the 2000s and 2010s, research expanded to explore L-ornithine’s potential benefits for immune function, gut health, and metabolic disorders. LOLA became more widely recognized as a standard treatment for hepatic encephalopathy in many countries, supported by multiple clinical trials and meta-analyses.

Current applications span from clinical use in liver disease to general wellness supplementation for exercise recovery, stress management, and sleep support. The evolution of L-ornithine usage reflects the growing understanding of its diverse roles in human metabolism and potential therapeutic applications beyond its fundamental role in the urea cycle.

Effects of L-ornithine supplementation on exercise-induced fatigue and recovery in trained athletes (ClinicalTrials.gov Identifier: NCT04123366), L-ornithine L-aspartate for prevention of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt (TIPS) placement (ClinicalTrials.gov Identifier: NCT03884959), Efficacy of L-ornithine L-aspartate in patients with non-alcoholic fatty liver disease (ClinicalTrials.gov Identifier: NCT04046926)