Ornithine L-aspartic acid

Other Names

(2S)-2-aminobutanedioic acid;(2S)-2,5-diaminopentanoic acid(4S)-4-amino-4-carboxybutan-1-aminium (2S)-2-amino-3-carboxypropanoate(S)-2,5-Diaminopentanoic acid compound with (S)-2-aminosuccinic acid (1:1)(S)-2,5-Diaminopentanoic acid L-aspartate salt2,5-Diaminopentanoic acid 2-aminobutanedioic acidAspartic acid, compd. with ornithine (1:1)L-Aspartic acid - L-ornithine (1:1)L-Aspartic acid, compd. with L-ornithine (1:1)L-Ornithine L-aspartateL-Ornithine L-aspartate saltL-Ornithine, L-aspartate (1:1)LOLAOrnithine asepartateOrnithine aspartateOrnithine aspartate [WHO-DD]Ornithine L-form aspartateOrnithine, L-, L-aspartate (1:1)ornithylaspartate

Synopsis

L-Ornithine L-Aspartate (LOLA): A Comprehensive Reference

1. Identity, Chemistry, and Natural Sources

L-Ornithine L-aspartate (LOLA) is a 1:1 stable salt of the naturally-occurring amino acids L-ornithine and L-aspartic acid. LOLA is a mixture of two endogenous amino acids. It is not a botanical extract or herb-derived compound; rather, it is a pharmaceutically synthesized salt whose two constituent amino acids are found throughout human and animal biochemistry. Hepa-Merz® combines two amino acids, L-ornithine and L-aspartate, and these active ingredients occur naturally in the body, playing important roles in liver metabolism and detoxification of the blood.

L-Ornithine (chemical name: (S)-2-amino-5-aminopentanoic acid) is a non-proteinogenic amino acid and a central intermediate of the hepatic urea cycle. L-Aspartic acid (chemical name: (S)-2-aminosuccinic acid) is a proteinogenic, non-essential amino acid that participates in numerous metabolic pathways including the citric acid cycle and purine synthesis. L-ornithine L-aspartate is a pharmaconutrient combining two non-essential amino acids.

The compound is also referred to by the following synonyms and abbreviations in the scientific and clinical literature: ornithine aspartate, ornithine-aspartate, L-ornithine-L-aspartate salt, and most commonly by the acronym LOLA. Its best-known proprietary pharmaceutical form is Hepa-Merz®, manufactured by Merz Pharma, Frankfurt, Germany.

Natural Sources of Constituent Amino Acids

A key function of the liver is the removal of excess blood-borne ammonia generated primarily from protein digestion in the intestines and carried to the liver via the portal vein. Both L-ornithine and L-aspartate are endogenously biosynthesized within human metabolic pathways — L-ornithine primarily through the urea cycle and from arginine, and L-aspartate through transamination of oxaloacetate. L-ornithine and L-aspartate are synthesized de novo in sufficient quantities in health; however, in conditions such as disease — including non-alcoholic liver disease (NAFLD) and urea cycle dysfunction — demand may exceed endogenous supply. LOLA as a product is not derived from a plant source but is manufactured as a pharmaceutical-grade salt.

Available Preparations and Dosage Forms

LOLA is available in both oral and parenteral forms. The main commercially available preparations include:

Granules for oral solution (sachets): One sachet with 5 g of granules contains 3 g L-ornithine L-aspartate. Excipients include citric acid, aspartame (E951), povidone 25, fructose, flavorings, and orange yellow S (E110).
Intravenous infusion concentrate (ampoules): One ampoule of 10 ml contains 5 g L-ornithine-L-aspartate as active substance, with water for injections as the excipient.
Oral over-the-counter supplement: LOLA is available in oral supplement form over the counter in many markets, while intravenous LOLA (Hepa-Merz) is available in Europe and other countries outside of the United States, obtainable with a prescription at a pharmacy and administered at an infusion center.

2. Traditional and Historical Use

LOLA does not arise from an ancient ethnobotanical tradition, nor is it described in classical herbal or Ayurvedic pharmacopoeias. Its history is rooted in 20th-century pharmaceutical development, not in folk medicine. L-ornithine L-aspartate (LOLA) has been known as an effective ammonia-lowering agent for more than 50 years with good evidence in hepatic encephalopathy. The compound was developed and brought to market by Merz Pharmaceuticals of Germany, which conducted a series of early clinical trials, some of which date to the late 1980s. Seventeen randomised clinical trials received funding and other support from pharmaceutical companies, with a number of early Merz-sponsored unpublished trials recorded from 1987 through the mid-1990s.

The clinical rationale for LOLA was grounded in the understanding of urea cycle biochemistry, which was established in the early 20th century. Once the role of ammonia as a major neurotoxin in hepatic failure was recognized in the mid-20th century, researchers explored amino acid substrates capable of activating ammonia removal. Merz Pharmaceuticals formulated LOLA as a stable salt preparation that could deliver both substrates simultaneously, producing the first branded product (Hepa-Merz) that gained regulatory approval in Germany and subsequently in many other countries in Europe, Asia, and Latin America.

Because LOLA is a pharmaceutical formulation rather than an herb or traditional remedy, there is no record of its use in traditional medicine systems such as Traditional Chinese Medicine, Ayurveda, or indigenous healing traditions. Its entire history of use is within the pharmaceutical and clinical medicine context of the 20th and 21st centuries.

3. Key Constituents and Active Compounds

LOLA readily dissociates into its constituent amino acids, L-ornithine and L-aspartate, which are readily absorbed by active transport, distributed, and metabolized. The compound functions as a prodrug-like system: its activity depends upon the independent and complementary biochemical roles of its two components within hepatic, muscular, and neural nitrogen metabolism.

L-Ornithine

Ornithine is a specific activator of ornithine carbamyl transferase and carbamylphosphate synthetase, and, in addition, is a substrate for ureagenesis. Being a urea cycle intermediate and, more specifically, an activator of carbamyl phosphate synthetase, L-ornithine stimulates ammonia removal as urea by periportal hepatocytes.

L-Aspartate

Aspartate and ornithine, after conversion to alfa-ketoglutarate, are substrates for glutamine synthesis, which is performed exclusively by a small population of perivenous hepatocytes, the so-called perivenous scavenger cells.

Downstream Metabolites

Both L-ornithine and L-aspartate are substrates for transamination reactions resulting in formation of glutamate, the obligate substrate for glutamine synthetase located in perivenous hepatocytes, skeletal muscle, and brain. Beyond ammonia-detoxification metabolites, mechanisms responsible for the beneficial effects of LOLA in NAFLD/NASH involve, in addition to its established ammonia-lowering effect, metabolic transformations of the LOLA-constituent amino acids L-ornithine and L-aspartate into L-glutamine, L-arginine, and glutathione.

4. Mechanisms of Action

4.1 Urea Cycle Activation

LOLA removes ammonia via two distinct mechanisms: by boosting the synthesis of urea, as ornithine and aspartate are substrates for argininosuccinate synthetase and ornithine transcarbamylase, and by increasing the synthesis of glutamine via the enzyme glutamine synthetase (GS). These reactions are carried out mainly in the periportal portion of the hepatic lobules.

4.2 Glutamine Synthesis in Skeletal Muscle and Brain

Transformations of the constituent amino acids of LOLA either via the hepatic urea cycle into urea per se, or into glutamine via glutamine synthetase expressed by perivenous hepatocytes, brain, and skeletal muscle, afford multiple pathways whereby ammonia is readily removed. The skeletal muscle pathway is of particular clinical relevance in patients with advanced cirrhosis, where liver capacity for urea synthesis is substantially reduced.

4.3 Hepatoprotective Mechanisms

Metabolic transformations of the LOLA-constituent amino acids into L-glutamine, L-arginine, and glutathione produce metabolites with well-established actions implicated in the prevention of lipid peroxidation, improvement of hepatic microcirculation, and anti-inflammatory and anti-oxidant properties. Studies in experimental chronic liver disease have demonstrated that treatment with LOLA led to a significant 2.5-fold increase of plasma L-arginine, and increases of circulating L-arginine have also been reported in patients with cirrhosis following treatment with LOLA.

4.4 Mitochondrial and Metabolic Effects

A 2024 cell-biology investigation found additional molecular targets relevant to NAFLD. In HepG2-based models of steatosis, insulin resistance, and metabolic syndrome, LOLA reduced the release of NH₃; beneficially modulated the expression of genes related to fatty acid import/transport (cd36, cpt1), synthesis (fasn, scd1, ACC1), and regulation (srbf1); reduced cellular ATP and acetyl-CoA; and favorably modulated the expression of master regulators/genes of energy balance/mitochondrial biogenesis (AMPK-α, pgc1α). Moreover, LOLA reconstituted the depolarized mitochondrial membrane potential, while retaining mitochondrial integrity and avoiding induction of superoxide production, with most effects being concentration-dependent at ≤40 mM LOLA. These findings are preclinical (cell-based) and require confirmation in clinical trials.

4.5 Pharmacokinetics

Systematic pharmacokinetic and pharmacodynamic studies in experimental models of liver failure and in patients have resulted in a clear understanding of the mechanisms that underpin the effective ammonia-lowering actions of LOLA. Following oral administration, LOLA is rapidly absorbed dependent on the Na⁺ ion gradient, and the elimination half-life is estimated to be in the 30–45 min range with bioavailability of 82.2%. After ingestion, LOLA disintegrates into its constituent amino acids and then is actively absorbed in the small intestine apical layer.

5. Body Systems and Health Areas Associated with LOLA

Hepatic system: Liver metabolism, ammonia detoxification, hepatic encephalopathy, hepatoprotection in cirrhosis, NAFLD/NASH
Central nervous system: Neurological complications of liver failure (hepatic encephalopathy), neuropsychiatric function
Skeletal muscle: Sarcopenia associated with chronic liver disease, muscle protein synthesis
Metabolic system: Nitrogen metabolism, urea cycle, glutamine synthesis, potential role in metabolic syndrome (emerging/preclinical evidence)

6. Scientific Evidence by Area of Use

6.1 Hepatic Encephalopathy (HE) — Overt Form

Hepatic encephalopathy (HE) is a potentially reversible functional disorder of the brain with neurological and psychiatric symptoms, occurring in up to 70% of patients with cirrhosis at some time during the course of disease; the chief neurotoxin implicated in the development of HE is ammonia.

Administration of L-ornithine L-aspartate (LOLA) improves mental status and decreases serum and spinal fluid ammonia levels by stimulating both the urea cycle and glutamine synthesis, which are key metabolic pathways in ammonia detoxification.

The landmark controlled trial in this area was conducted by Kircheis et al. and published in Hepatology in 1997. A meta-analysis identified high-quality randomized controlled trials of LOLA among a total of 212 patients with chronic Stage I and II HE; the largest included trial, with 126 patients, evaluated the effects of intravenous dosing, while the others studied the drug's oral formulation, and all concluded that LOLA improved symptoms of clinically overt encephalopathy relative to either lactulose or placebo.

A 2013 meta-analysis of eight RCTs involving 646 patients found that when comparing placebo/no-intervention control, LOLA was significantly more effective in the improvement of HE in the total (RR: 1.49, 95% CI: 1.10 to 2.01), overt HE (RR: 1.33, 95% CI: 1.04 to 1.69), and minimal HE patients.

A comprehensive appraisal by Butterworth and McPhail (2019) concluded that meta-analyses of RCTs conducted over the last two decades generally reveal evidence of benefit of LOLA in a range of clinical presentations, including improvement of mental state grade in overt HE (OHE) assessed by West Haven criteria as well as in minimal HE (MHE) assessed by psychometric testing, where the oral formulation of LOLA was determined to be particularly effective. However, concerns over study quality were noted in one meta-analysis. Nevertheless, the concomitant lowering of fasting blood ammonia was reported in all RCTs using this endpoint. Network meta-analyses showed that LOLA appears to be comparable (or superior) in efficacy to non-absorbable disaccharides or probiotics.

A 2025 systematic review and meta-analysis including 12 RCTs and 858 patients evaluated LOLA combined with lactulose, finding that in terms of total effective rate (RR: 1.31, 95% CI: 1.22–1.42), the result was statistically significant, with corresponding significant improvements also for AST, ALT, NH₃, and TBIL (all p = 0.00001).

Limitations and contradictory evidence: The 2018 Cochrane systematic review by Goh et al. raised important methodological concerns. L-ornithine L-aspartate had a beneficial effect on mortality compared with placebo or no intervention when including all trials (RR 0.42, 95% CI 0.24 to 0.72; 19 trials; 1489 participants; very low quality evidence), but not when the analysis was restricted to the trials at low risk of bias (RR 0.47, 95% CI 0.06 to 3.58; 4 trials; 244 participants). Similarly, it had a beneficial effect on hepatic encephalopathy when including all trials (RR 0.70, 95% CI 0.59 to 0.83; 22 trials; 1375 participants; very low quality evidence), but not in the one trial at low risk of bias (RR 0.96, 95% CI 0.85 to 1.07; 63 participants). The Cochrane review therefore rated the overall quality of evidence as very low. The efficacy of oral LOLA has been a subject of debate, as the AASLD-EASL clinical guidelines suggested that oral supplementation with LOLA is not effective; recent meta-analyses suggest that LOLA has beneficial effects on HE, decompensation, and mortality, but one stated that the quality of evidence was very low, leaving the potential beneficial effect of LOLA uncertain.

A 2009 critical review similarly noted that although trials have shown efficacy of LOLA in reducing hyperammonemia of hepatic encephalopathy, sufficient evidence of a significant beneficial effect on patients was not found; the studies performed were small, with short follow-up periods, and half of them showed low methodological quality.

6.2 Minimal Hepatic Encephalopathy (MHE)

Minimal hepatic encephalopathy (MHE) is an early stage of hepatic encephalopathy and is highly prevalent; the efficacy of LOLA for the treatment of HE is well known, but its role in MHE remained uncertain until recently. A 2024 meta-analysis searched multiple databases for RCTs from inception through January 2023 and included six RCTs comprising 292 patients; compared with placebo or no intervention, LOLA was more effective in reversing MHE (RR = 2.264, 95% CI = 1.528–3.352, p = 0.000, I² = 0.0%).

6.3 Prevention and Prophylaxis of Overt Hepatic Encephalopathy

A 2019–2020 systematic review and meta-analysis by Butterworth specifically examined LOLA's role in preventing or delaying the onset of OHE. Using established inclusion/exclusion criteria, six RCTs for a total of 384 patients were identified, five of which were of high quality and low risk of bias according to Jadad-Cochrane criteria. Treatment with LOLA resulted in significant reductions in the risk of progression to OHE in MHE patients (3 studies) with RR: 0.23 [95% CI: 0.07, 0.73], p < 0.01. LOLA was also effective for secondary OHE prophylaxis with RR: 0.389 [95% CI: 0.174–0.870] p < 0.002, as well as for primary prophylaxis for OHE following acute variceal bleeding with RR: 0.42 [95% CI: 0.16–0.98] p < 0.03, and for OHE prophylaxis post-TIPSS with RR: 0.30 [95% CI: 0.03–2.66] compared to placebo/no intervention. Both oral and intravenous formulations of LOLA appeared to be effective for the prevention of progression to OHE in patients with MHE.

6.4 Post-TIPSS Hepatic Encephalopathy Prevention

Transjugular intrahepatic portosystemic shunt (TIPSS) procedures are associated with increased ammonia levels and elevated HE risk. A randomized clinical trial by Bai et al. (2014) investigated LOLA specifically in this context. TIPSS use is associated with increases in ammonia concentration and HE risk; patients were randomised to receive LOLA or no-LOLA treatment for 7 days, with fasting and post-prandial venous ammonia levels as primary outcomes, and psychometric performance, post-TIPSS HE, and liver and renal function as secondary outcomes.

6.5 Intravenous versus Oral Administration

A 2024 randomized comparative study by Jhajharia et al. directly compared IV vs. oral LOLA in patients with overt HE. The study compared the efficacy of intravenous versus oral LOLA in 40 patients with chronic liver disease and overt HE, randomly assigned in a 1:1 ratio, with HE grading and serum ammonia levels monitored from day 1 to day 5. The mean difference in ammonia levels from day 1 to day 5 was 55.4 ± 32.58 µmol/L in the IV LOLA group and 60.75 ± 13.82 µmol/L in the oral LOLA group (p = 0.511), with significant reductions in ammonia levels observed from day 1 to day 5 within each group (p < 0.001). This small trial suggested no statistically significant difference between routes of administration, though the study's size limits strong conclusions.

6.6 Quality of Life in Cirrhotic Patients with HE

An open-label, prospective, multicentre observational study evaluated health-related quality of life (HR-QOL) in cirrhotic patients treated with oral LOLA. L-ornithine-L-aspartate was administered over a period of 8 weeks. Treatment with L-ornithine-L-aspartate for 8 weeks markedly improved all HR-QOL domains, in particular fatigue (67.5% improvement), and symptom severity also improved, with particular benefits seen in fatigue, sleep quality, and concentration deficits. Physicians rated 70.0% of patients very much or much improved at the end of treatment. Very good or good tolerability was observed in 97.8% of patients. No drug-related adverse events were reported. This study is observational, limiting its interpretability.

6.7 Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH)

While LOLA has been used in cirrhosis and acute liver injury settings, it is less clear if LOLA could be used in NAFLD; NAFLD and the progressive form NASH are currently the leading causes of chronic liver disease worldwide, with roughly 25% of the world population affected by NAFLD, with consequences including end-stage liver disease and cardiovascular morbidity and mortality.

Evidence from a multicenter RCT revealed that LOLA has hepatoprotective properties in patients with fatty liver of diverse etiology, and 12 weeks treatment with oral LOLA (6–9 g/d) results in a dose-related reduction in activities of liver enzymes and triglycerides together with significant improvements of liver/spleen CT ratios. A preliminary report also described improvements of hepatic microcirculation in patients with NASH following treatment with LOLA.

The proposed hepatoprotective mechanisms include metabolic transformations of the LOLA-constituent amino acids L-ornithine and L-aspartate into L-glutamine, L-arginine, and glutathione, with these metabolites having well-established actions implicated in the prevention of lipid peroxidation and improvement of hepatic microcirculation, in addition to anti-inflammatory and anti-oxidant properties. Further assessments in the clinical setting are required before firm conclusions about LOLA's role in NAFLD/NASH management can be drawn.

6.8 Sarcopenia in Chronic Liver Disease

Studies in experimental animals and in patients demonstrate that ammonia is directly implicated in the pathogenesis of sarcopenia in cirrhosis via mechanisms involving increased expression of myostatin and of autophagy markers such as LC3 lipidation and p62, leading to muscle dysmetabolism and sarcopenia. Paradoxically, skeletal muscle replaces liver as the primary ammonia-detoxifying site as a result of modification of genes coding for key proteins in ammonia-lowering pathways in cirrhosis. Thus, a vicious cycle occurs whereby hyperammonemia causes severe muscle damage and sarcopenia that, in turn, limits the capacity of muscle to remove excess blood-borne ammonia.

Randomized clinical trials and meta-analyses confirm that LOLA is an effective ammonia-lowering agent that stimulates both urea synthesis by residual hepatocytes and muscle glutamine synthesis; treatment of cirrhotic patients with LOLA limits ammonia-induced sarcopenia by improving muscle protein synthesis and function, and it is conceivable that the antisarcopenic action of LOLA contributes to its efficacy for the treatment of HE in cirrhosis. Recent studies also provide evidence to suggest that LOLA may have hepatoprotective properties and may assist in the prevention of sarcopenia in patients with cirrhosis.

6.9 Metabolic Syndrome and Insulin Resistance — Emerging Preclinical Evidence

A 2024 study published in Pharmaceutics investigated LOLA's molecular targets in cell models of NAFLD-related metabolic dysfunction. In HepG2-based models of steatosis, insulin resistance, and metabolic syndrome, LOLA reduced the release of NH₃ and beneficially modulated the expression of genes related to fatty acid import/transport, synthesis, and regulation, while favorably modulating the expression of master regulators/genes of energy balance and mitochondrial biogenesis (AMPK-α, pgc1α). The authors demonstrate for LOLA a broad range of reconstituting effects on metabolic carriers and targets of catabolism/energy metabolism impaired in NAFLD. LOLA also ameliorated the deleterious psychometric effects of glutamine in Child's grade B and C patients with cirrhosis without transjugular intrahepatic portosystemic shunts. These findings are based on cell lines and require prospective clinical trials before any conclusions about metabolic syndrome treatment can be drawn.

7. Dosage Forms and Dosages Reported in Clinical Studies

Oral Formulation

When taken by mouth, L-ornithine-L-aspartate is possibly safe when used in doses of up to 18 grams daily for up to 6 months.
In the NAFLD multicenter RCT: oral LOLA at 6–9 g/d for 12 weeks.
In the oral HE studies referenced in a DARE meta-analysis: LOLA administered orally in doses of 3 g or 6 g three times a day.
The Hepa-Merz granule sachet contains 3 g LOLA per 5-g sachet; 1–2 sachets dissolved in a large amount of fluid (e.g., a glass of water or juice) are taken orally three times a day during or after meals.

Intravenous Formulation

The recommended IV dose is up to 20 g (4 ampoules) daily. In cases of loss of consciousness (pre-coma) and clouding of consciousness (coma), up to 8 ampoules within 24 hours, depending on the severity of the condition.
In IV studies: intravenous infusions of 20 g over four hours were used in included RCTs.
Adverse reactions may occur rarely in the form of mild gastrointestinal disturbances; to prevent such reactions, a maximum infusion rate of 5 g LOLA infusion concentrate per hour is recommended.
LOLA infusion concentrate can be added to conventional IV fluids (0.9% Sodium Chloride, 5% Dextrose, Ringer's lactate). The normal dilution rate is 1 ampoule per 100 ml of IV fluid; however, the dose should not exceed 6 ampoules per 500 ml infusion.

Duration

The duration of the included clinical studies was typically one or two weeks for most acute HE trials, while the NAFLD RCT used 12 weeks of treatment, and one quality-of-life observational study administered LOLA over a period of 8 weeks.

8. Safety Considerations and Interactions

8.1 General Tolerability

LOLA therapy is generally very well tolerated and adverse reactions may occur rarely, in the form of mild gastrointestinal disturbances. Adverse reactions reported in the literature are mostly concentrated in the gastrointestinal and cardiocerebrovascular systems; as LOLA is a hypertonic solution, rapid infusion or high oral doses can increase intestinal osmotic pressure, stimulate intestinal peristalsis, and lead to diarrhea and abdominal pain.

8.2 Electrolyte Disturbances at High Doses

High doses may consume blood ammonia through the urea cycle, leading to hypokalemia or hyponatremia, potentially triggering arrhythmias or blood pressure fluctuations. Ornithine metabolism may produce nitric oxide (NO), causing vasodilation and resulting in transient hypotension or dizziness.

8.3 Renal Impairment — Absolute Contraindication

Consistent with its mechanism of action, LOLA leads to the increased formation of urea, which has to be eliminated via the kidneys; LOLA should therefore not be used in cases where there is severe impairment of renal function. The absolute contraindication is severe renal impairment (renal failure), and a serum creatinine level in excess of 3 mg/100 ml can be taken as a guide. At high doses of Hepa-Merz infusion concentrate, serum and urine urea levels should be monitored.

8.4 Pregnancy and Lactation

There are no clinical data available on the use of Hepa-Merz Infusion concentrate in children and during pregnancy; L-ornithine L-aspartate has been investigated for reproduction toxicity only to a limited extent in experimental animal studies, and its administration in pregnancy should therefore be avoided. If treatment is nevertheless thought to be necessary, the benefits and risks should be carefully assessed. It is not known whether L-ornithine L-aspartate passes into breast milk.

8.5 Hypersensitivity

An absolute contraindication exists for hypersensitivity to L-ornithine-L-aspartate, orange yellow S, or any of the other excipients in the granule formulation.

8.6 Fructose-Containing Excipients

Hepa-Merz Granules contain fructose; patients with rare hereditary problems of fructose intolerance should not take this medicine. Each sachet of Hepa-Merz Granules contains 1.13 g of fructose (corresponding to approximately 0.11 BU), a consideration for diabetic patients.

8.7 Known Drug Interactions

No formal interaction studies have been performed, and up to now interactions are not known. It has been postulated that the co-administration of gut-acting ammonia-lowering agents such as lactulose, rifaximin, or probiotics may have additive or complementary effects on blood ammonia reduction, as these agents target different steps of ammonia metabolism; however, no formal drug–drug interaction data from controlled studies are available for LOLA.

8.8 Aspartate Accumulation — A Noted Research Concern

A research-level concern identified in one patent-related investigation noted that the aspartate component of LOLA may accumulate in the body, and this accumulation of aspartate may be harmful to patients since aspartate worsens the effect of ammonia on neutrophil function, further reducing neutrophil function. This concern is speculative and has not been reported as a clinical adverse outcome in RCTs of LOLA; it is not reflected in the approved prescribing information for Hepa-Merz.

9. Regulatory Status and Clinical Position

Intravenous LOLA (Hepa-Merz) is available in Europe and other countries outside of the United States. Its therapeutic indications include the treatment of concomitant disease and sequelae due to impaired detoxification activity (e.g., in cirrhosis of the liver) with the symptoms of latent and manifest hepatic encephalopathy. More than 30 studies have been published in the setting of HE that compare LOLA to placebo, lactulose, antibiotics, probiotics, or branched-chain amino acids (BCAAs). Despite this body of evidence, the overall evidence base remains contentious: the results pooled in a meta-analysis of 33 RCTs did not reveal any beneficial effect of LOLA over the other treatments, mainly because of bias related to the studies. The most comprehensive independent assessment, the 2018 Cochrane Review, rated the available evidence as very low quality, emphasizing that adequately powered, low-bias trials are still needed to establish definitive clinical recommendations.

References

Health Conditions

Health conditions that Ornithine L-aspartic acid may help support.

No conditions available.

Body Systems

Body systems that Ornithine L-aspartic acid may help support.

No body systems available.