L-ornithine L-aspartate Research Articles

Quantification of L-ornithine L-aspartate in health supplement by HPLC in combination with o-phthalaldehyde derivative technique

Dietary supplements containing L-ornithine L-aspartate (LOLA) are on the rise. Thus, a simple, reliable method of analysis for determining LOLA has been developed, which helps to control product quality. In this study, a method for determining LOLA in dietary supplements by HPLC in combination with o-phtalaldehyde derivatives (OPA) was developed and validated. The study optimized conditions for extraction of LOLA from the matrix, then derived with OPA and chromatographic separation on column C18. The detection limits and quantitative limits of the method were conducted on low-content real samples, with LOD and LOQ values achieved at 6.0 and 20.0 μg/g, respectively. The method has good recovery (98 – 106%) and repeatability (1.32 – 3.50%) that meet the method performance requirements according to AOAC. The validated method has been applied to analyze LOLA content in dietary supplements at the National Institute for Food Control.

Unusual Presentation of Confusion: Hyperammonaemic Hepatic Encephalopathy Due To Intrahepatic Portosystemic Venous Shunt In An Older Patient

Abstract Background Delirium is an acute, usually reversible neuropsychiatric syndrome and often presents as confusion, especially in the older population. Early detection and management of causes is vital to reduce mortality, morbidity, and long-term cognitive status decline. Intrahepatic portosystemic venous shunts are rare vascular malformations. These malformations can be congenital or acquired and may manifest as heart failure, hepatic encephalopathy, or pulmonary hypertension. Methods A 75-year-old man presented to the emergency department with a 5-week history of confusion, daytime somnolence, and fatigue. His physical examination was unremarkable. His symptoms were initially thought to be due to sub-optimally controlled Obstructive Sleep Apnoea. Nevertheless, his confusion progressed further during admission and required admission to the intensive care unit and intubation. Investigations initially showed deranged Liver function tests. Extensive investigations were done, including CT brain, MRI brain, septic screen, Arterial blood gas, and Lumbar puncture, which were all inconclusive. An Electroencephalogram was suggestive of Encephalopathy. His Ammonia level was high (123). Further investigations, Triphasic CT liver, revealed Intrahepatic portosystemic venous shunt and was diagnosed with hyperammonaemic hepatic encephalopathy due to Intrahepatic portosystemic venous shunt. Results Management included the commencement of lactulose, rifaximin, and L-ornithine L-aspartate (LOLA). An IR-guided embolisation of the porto-venous shunt was performed. At two-months review, the patient reported no further episodes of confusion. Conclusion Intrahepatic portosystemic venous shunts should be considered in the differential diagnosis of patients presenting with confusion or other unexplained neurological symptoms, especially in the presence of liver dysfunction. Early diagnosis and appropriate management are crucial for favourable outcomes.

L-Ornithine-l-Aspartate (LOLA) Normalizes Metabolic Parameters in Models of Steatosis, Insulin Resistance and Metabolic Syndrome.

l-Ornithine- l-aspartate (LOLA) reduces toxic ammonium (NH3) plasma levels in hepatic encephalopathy. NH3 detoxification/excretion is achieved by its incorporation into urea and glutamine via activation of carbamoyl phosphate synthetase 1 (CSP1) by l-ornithine and stimulation of arginase by l-aspartate. We aimed at identifying additional molecular targets of LOLA as a potential treatment option for non-alcoholic fatty liver disease (NAFLD). In primary hepatocytes from NAFLD patients, urea cycle enzymes CSP1 and ornithine transcarbamylase (OTC) increase, while the catabolism of branched-chain amino acids (BCAAs) decreases with disease severity. In contrast, LOLA increased the expression rates of the BCAA enzyme transcripts bcat2, bckdha, and bckdk. In untreated HepG2 hepatoblastoma cells and HepG2-based models of steatosis, insulin resistance, and metabolic syndrome (the latter for the first time established herein), 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. Most effects were concentration-dependent at ≤40 mM LOLA. We demonstrate for l-ornithine-l-aspartate a broad range of reconstituting effects on metabolic carriers and targets of catabolism/energy metabolism impaired in NAFLD. These findings strongly advocate further investigations to establish LOLA as a safe, efficacious, and cost-effective basic medication for preventing and/or alleviating NAFLD.

Prophylaxis of hepatic encephalopathy: current and future drug targets.

Hepatic encephalopathy is described by a broad spectrum of neurological and psychiatric aberrations resulting due to advanced liver dysfunction. It is a neurological disorder due to hepatic insufficiency and/or portosystemic shunts. Its clinical presentation includes neuropsychiatric dysfunction ranging from subclinical changes to comatose state. It is a sign of poor prognosis in cirrhotics with a high 1-year mortality. Each episode of hepatic encephalopathy leads to high hospitalization rate, poor prognosis and raised burden of healthcare. Primary prophylaxis is prevention of initial occurrence and secondary prophylaxis is prevention of reappearance of hepatic encephalopathy in subjects who had prior history. Early detection and management of triggers is very important in the treatment of hepatic encephalopathy. The initial choice of treatment is still lactulose, as it is effective in minimal, overt, and recurrent hepatic encephalopathy. Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated. Branch chain amino acids are beneficial in subjects who are protein intolerant. L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy. Rifaximin along with lactulose is effective in managing overt and recurrent hepatic encephalopathy. Large portosystemic shunts embolization and liver transplant is efficacious in certain group of patients. Nutritional therapy and fecal microbiota transplantation are newer therapies for hepatic encephalopathy but the evidences are limited, more research is required to prove their efficacy. Involvement of hospital pharmacists, telemedicine, and providing education are also beneficial in managing hepatic encephalopathy.

Efficacy and safety of intravenous L-ornithine L-aspartate in patients with grade III and IV hepatic encephalopathy

Efficacy and safety of intravenous L-ornithine L-aspartate in patients with grade III and IV hepatic encephalopathy

Safety of non-standard regimen of systemic steroid therapy in patients with Graves' orbitopathy: a single-centre experience.

Graves' orbitopathy (GO) is an autoimmune disorder of the orbit and retro-ocular tissues and the primary extrathyroidal manifestation of Graves' disease. In moderate-to-severe and active GO iv glucocorticoids (GCs) are recommended as first-line treatment. The aim was to assess the safety profile of methylprednisolone administered intravenously for three consecutive days at 1g in patients with active, moderate-to-severe or sight-threatening Graves' orbitopathy. We retrospectively evaluated 161 medical records of patients with GO treated with high-dose systemic GCs in the Department of Endocrinology, Metabolic Disorders, and Internal Medicine in Poznań between 2014 and 2021. Clinical data included age, gender, laboratory results, activity and severity of GO, smoking status, disease duration, and presented side effects. The presence of mild side effects was observed during 114 (71%) hospitalizations. The most common complications were hyperglycemia (n = 95) and elevated aminotransferases (n = 31). Increased levels of aminotransferases were more likely observed in smokers and GO duration above 12months. Based on the multivariate logistic regression, higher TRAb and CAS values were significantly associated with lower odds of hyperglycemia. In turn, the increased odds of elevated aminotransferases were significantly correlated with higher initial ALT levels, female gender, and GO duration above 12months. In addition, the multidimensional correspondence analysis (MPA) showed that GO patients who declared smoking and had not L-ornithine L-aspartate applied demonstrated a higher probability of elevated aminotransferases. Active GO treatment with high-dose systemic GCs is not associated with serious side effects. Hyperglycemia is the most common steroid-induced complication.

Hyperammonemia as a manifestation of post-covid syndrome in patients with nonalcoholic fatty liver disease: post-hoc analysis of the LIRA - COVID observational clinical program

Post-Covid syndrome (PCS) is considered as a consequence of a previous coronavirus infection. The liver in COVID-19 is one of the most frequently affected organs, with the development of asthenia, cognitive impairment, as well as increased activity of alanine and aspartic transaminases (ALT and AST), which persist in some patients up to 4-6 months after discharge from the hospital. The cause of asthenia may be hyperammonemia (HA), which in COVID-19 is a manifestation of liver dysfunction against the background of the direct cytotoxic effect of SARS-CoV-2 on hepatocytes, which was previously shown as part of the clinical observational program protocol “LIRA - COVID”. Due to the great relevance of the problem of the combination of PCS, non-alcoholic fatty liver disease (NAFLD) and HA a post-hoc analysis of the observational clinical program LIRA - COVID was carried out. It was shown that NAFLD has a significant effect on the level of AST before the start of treatment with L-ornithine - L-aspartate (LOLA). The presence of NAFLD has a significant effect on ammonia levels after 14 days of treatment, since in the group of patients with NAFLD the ammonia level was significantly higher than in the group without NAFLD. It was concluded that it is advisable to include in the examination scheme of patients with PCS and NAFLD, determination of the level of ammonia in the blood, when elevated, the administration of the drug to such patients is justified LOLA course for 4 weeks at a standard dose of 9 g per day.

A Comprehensive Overview of the Past, Current, and Future Randomized Controlled Trials in Hepatic Encephalopathy.

Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.

S1478 Efficacy of L-Ornithine L-Aspartate as a Stand-Alone Treatment for Hepatic Encephalopathy in Patients With Cirrhosis - A Systematic Review and Meta-Analysis

S1478 Efficacy of L-Ornithine L-Aspartate as a Stand-Alone Treatment for Hepatic Encephalopathy in Patients With Cirrhosis - A Systematic Review and Meta-Analysis

P30 L-Ornithine L-Aspartate [LOLA] Improves Both Severe Encephalopathy and Survival in Patients With Liver Cirrhosis: Results of RCTs, Systematic Reviews and Meta-Analyses

P30 L-Ornithine L-Aspartate [LOLA] Improves Both Severe Encephalopathy and Survival in Patients With Liver Cirrhosis: Results of RCTs, Systematic Reviews and Meta-Analyses

Efficacy of L-Ornithine L-Aspartate in Recovery of Patients Suffering from Acute Viral Hepatitis

Objective: To assess the efficacy of L-Ornithine L-Aspartate (LOLA) compared with non-LOLA Group in the recovery of patients with acute viral hepatitis.
 Study Design: Quasi-experimental study.
 Place and Duration of Study: Department of General Medicine, Railway Hospital, Rawalpindi Pakistan, from Aug 2020 to Jan 2021.
 Methodology: All patients of either gender, aged >18 years with acute viral hepatitis were included. All patients were divided into two groups. LOLA-Group (Group-A) was given as an infusion over 24 hours at a dosage of 300 grams for three consecutive days. Whereas Group-B had patients to whom L-Ornithine L-Aspartate (LOLA) was not administered. The efficacy was defined as no signs and symptoms in comparison to baseline (clinical improvement), LFTs improved to more than half compared to baseline, and INR was <1.2 at seven days’ follow-up.
 Results: Of 128 patients, the median age was 28 years (20-32). A significant median difference in total bilirubin on the seventh day (p-value 0.044) was observed for the L-Ornithine L-Aspartate (LOLA)-Group. In addition, the efficacy was found to be significantly higher among patients in the Control Group as compared to the patients in the Treatment Group, i.e., 54(84.4%) and 40(62.5%), respectively (p-value 0.005).
 Conclusion: This study showed that the outcome of L-Ornithine L-Aspartate (LOLA) is not very effective in managing patients with acute viral hepatitis.

ASSESSMENT OF THE INFLUENCE OF COMPLEX TREATMENTS ON KIDNEY FUNCTIONAL RESERVE IN PATIENTS WITH LIVER CIRRHOSIS DEVELOPED DUE TO HEPATITIS V AND C.

Cirrhosis of the liver is manifested by necrosis of hepatocytes, disruption of its normal architecture due to diffuse growth of connective tissue and the formation of regeneration nodules, as well as developing fibrosis. The article presents a modern approach to the treatment of hepatorenal syndrome, one of the severe complications of the disease. The effect of eplerenone, L-ornithine L-aspartate and glutathione drugs on the functional reserve of kidneys was evaluated on the basis of complex treatment.

Results of a multicenter prospective observational study “Clinical significance of hyperammonemia in patients with post-Covid syndrome (LIRA - COVID)”: efficacy of L-ornithine L-aspartate

Epidemiological data suggests that approximately 10-65% of patients with mild to moderate COVID-19 have persistent symptoms already after an acute infection, which may last for six months or more. Previous clinical studies have shown that similar symptoms may also occur in the liver. Russian scientists have studied the phenomenon of hyperammonemia in the acute phase of COVID-19, but the problem of elevated blood ammonia levels in post - COVID syndrome has not been studied before. One possible option for the correction of hyperammonemia is the L-ornithine - L-aspartate (LOLA) preparation. The aim of the study was to investigate the manifestation of hyperammonemia in post - COVID syndrome and the possibility of its correction by using LOLA. Eighty-three patients (mean age 51.71 ± 12.82) with post-COVID syndrome, attention and memory impairment, chronic fatigue, hyperammonemia, 2-fold increase of alanine transaminase (ALT) and aspartate transaminase (AST) levels were included into multicenter, prospective observational study. L-ornithine-L-aspartate (LOLA) was given (3 g 3 times per day orally) for 4 weeks to correct hyperammonemia. Patients were accessed by the number connection test (NCT), fatigue evaluation test, measurement of ammonia and ALT, AST levels at baseline, and after 4 weeks. At week 4 the ammonia level was significantly decreased in 81 patients (97.6%). Time (sec) to complete the NCT was 49,43 ± 15,85 vs 64.67 ± 24.95 at baseline (p<0.001). Before treatment, the majority of patients had stage 1 hepatic encephalopathy (HE) - 50.6% and stage 1-2 (intermediate) HE - 30.1%, stage 2 HE - 10.9%, stage 3 HE - 2.4%. After LOLA treatment, the distribution changed: 41% of patients had no HE, 36.1% had stage 1 of HE, 22.9% had stage 1-2 (intermediate) of HE, and stage 2 and 3 of HE was no longer defined. The mean score in fatigue evaluation test was 46,27 ± 10.0 vs 64,71 ± 19,18 at baseline (p<0.001). ALT and AST levels were 47,83 ± 38,21 units/l vs 95,75 ± 68.99 units/l at baseline and 40,10 ± 35,97 units/l vs 78,51 ± 90,90 units/l at baseline respectively (p<0.001). This study showed that the inclusion of LOLA in a dose of 3 g 3 times a day for 4 weeks was associated with significant improvement in the objective and subjective outcomes in patients with post-COVID syndrome.

Efficacy of probiotics in the treatment of minimal hepatic encephalopathy: A systematic review and meta-analysis.

Patients with minimal hepatic encephalopathy (MHE) have no recognizable clinical symptoms of hepatic encephalopathy (HE), but the mild cognitive and psychomotor deficits have been shown to negatively affect their daily functioning and quality of life. Treatment with probiotics has shown benefit in some clinical trials. This review aimed to systematically analyze the efficacy of probiotics in the treatment of MHE. A systematic search of the electronic databases PubMed, Science Direct, and Cochrane Library was conducted for randomized controlled trials (RCTs) in adult patients with MHE who had been given probiotics intervention. The primary outcomes were reversal of MHE and improvement of neuropsychometric tests, while the secondary outcome was the reduction of serum ammonia. Nine RCTs involving 776 MHE patients were included, consisting of 311 patients receiving probiotics and 465 patients receiving comparator (placebo or no treatment, lactulose, L-ornithine L-aspartate [LOLA], or rifaximin). The meta-analysis showed that probiotics significantly reversed MHE (OR = 3.95, p < 0.0001, 95% CI: 2.05 to 7.60) compared with placebo or no treatment. Probiotics also significantly reduced serum ammonia compared with placebo (pooled mean difference -25.94, p = 0.04, 95% CI: -50.21 to -1.66). However when compared to lactulose and LOLA, probiotics did not show a significant difference in reversal of MHE or reduction of serum ammonia levels. Probiotics were more effective in reversal of MHE and reduced serum ammonia levels in patients with MHE compared to placebo or no treatment, but not more effective than lactulose or LOLA.

Hyperammonemia in a septic patient with Ureaplasma parvum arthritis: a case report

BackgroundSeptic arthritis requires prompt diagnosis and treatments. Rare pathogens should be considered when patients respond poorly to the initial antibiotic treatments. Ureaplasma parvum is an opportunistic pathogen that commonly resides in the human urogenital tract. Its infection commonly causes hyperammonemia. Hyperammonemia from Ureaplasma parvum septic arthritis has never been reported previously.Case presentationA 65-year-old male presented with fever and left lower leg pain and swelling for more than ten days. Septic arthritis and sepsis were considered after laboratory tests and arthrocentesis. However, he responded poorly to the antibiotic treatments, including cefoperazone-sulbactam, imipenem-cilastatin, and linezolid. His mental status deteriorated rapidly with elevated blood ammonia levels with unremarkable liver function test and sonogram examination results. Despite the treatments with lactulose, L-ornithine L-aspartate, mannitol, and hemodialysis therapy to lower his ammonia level, his blood ammonia level remained persistently high. Finally, metagenomic sequencing of the left knee synovial fluid reported Ureaplasma parvum, which was considered to contribute to his hyperammonemia.ConclusionUreaplasma parvum could cause septic arthritis with hyperammonemia. Genetic tests, such as polymerase chain reaction and next-generation sequencing techniques, could provide a sensitive and fast diagnosis of Ureaplasma parvum.

A Simple Algorithm for Semiquantitative Analysis of Scored Histology Data in the R Environment, on the Example of Murine Non-Alcoholic Steatohepatitis Pharmacotherapy

Despite the high medical and socioeconomic burden of non-alcoholic fatty liver disease (NAFLD), treatments that could effectively reduce histological liver damage in this condition are lacking. As providing only qualitative data is a major limitation of most histological scoring systems, we aimed to develop a simple and straightforward algorithm for semiquantitative analysis of scored histology data using the extended Fisher’s exact test in the R environment. As an illustrative example, we used the effects of L-ornithine L-aspartate (LOLA) and empagliflozin (EMPA) in a 3-month chemical/dietary murine model of NAFLD. 100 C57Bl/6 mice were randomized into 4 groups: Intact (n = 10), Control (NAFLD; n = 30), LOLA (NAFLD + 1.5 g·kg−1 b.w./d LOLA orally; n = 30), and EMPA (NAFLD + 10 mg·kg−1 b.w./d EMPA orally; n = 30). LOLA reduced hepatitis activity (p &lt; 0.05), cholestasis, necrosis, and fibrosis severity (p &lt; 0.01), and EMPA prevented necrosis (p &lt; 0.05) and reduced fibrosis severity (p &lt; 0.01). The statistical approach we suggest can be used as a simple complementary tool for exploratory analysis of scored histology data.

Short-term efficacy and safety of l-ornithine l-aspartate therapy in patients with cirrhosis and minimal hepatic encephalopathy: a real-life cohort study

Short-term efficacy and safety of l-ornithine l-aspartate therapy in patients with cirrhosis and minimal hepatic encephalopathy: a real-life cohort study

Impact of L-ornithine L-aspartate on non-alcoholic steatohepatitis-associated hyperammonemia and muscle alterations.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in the world. Progression toward non-alcoholic steatohepatitis (NASH) is associated with alterations of skeletal muscle. One plausible mechanism for altered muscle compartment in liver disease is changes in ammonia metabolism. In the present study, we explored the hypothesis that NASH-associated hyperammonemia drives muscle changes as well as liver disease progression. In Alms1-mutant mice (foz/foz) fed a 60% fat diet (HFD) for 12 weeks; we investigated hepatic and muscular ammonia detoxification efficiency. We then tested the effect of an 8 week-long supplementation with L-ornithine L-aspartate (LOLA), a known ammonia-lowering treatment, given after either 4 or 12 weeks of HFD for a preventive or a curative intervention, respectively. We monitored body composition, liver and muscle state by micro computed tomography (micro-CT) as well as muscle strength by four-limb grip test. According to previous studies, 12 weeks of HFD induced NASH in all foz/foz mice. Increase of hepatic ammonia production and alterations of urea cycle efficiency were observed, leading to hyperammonemia. Concomitantly mice developed marked myosteatosis. First signs of myopenia occurred after 20 weeks of diet. Early LOLA treatment given during NASH development, but not its administration in a curative regimen, efficiently prevented myosteatosis and muscle quality, but barely impacted liver disease or, surprisingly, ammonia detoxification. Our study confirms the perturbation of hepatic ammonia detoxification pathways in NASH. Results from the interventional experiments suggest a direct beneficial impact of LOLA on skeletal muscle during NASH development, though it does not improve ammonia metabolism or liver disease.

Effects of Ornithine Aspartate and Empagliflozin on Memory Deficit Symptoms in Experimental Steatohepatitis

In this study, L-ornithine L-aspartate and empagliflozin were evaluated in terms of their potential effects on the hippocampus-dependent memory status in non-alcoholic steatohepatitis (NASH) in C57Bl/6 mice. NASH was found to be associated with an early transient decrease in the short-term recognition memory as well as a progressive reduction in the short-term spatial memory. L-ornithine L aspartate effectively prevented the impairment of recognition, rather than spatial, memory. At the same time, empagliflozin failed to improve the memory status of the animals.

Prospects for the use of hepatotropic LOLA therapy in veterinary practice

Relevance. There are enough works devoted to the LOLA therapy in treatment ofhepatopathy of various origins, however, these works are devoted to research in medicine or in laboratory studies of animals.Methods. For inclusion in the experiment, screening studies of the blood plasma of horses for the level of gamma-glutamyltransferase were carried out. The inclusion criteria was the value of the activity of glutamyltransferase in blood serum more than 22 U/l (upper limit of the reference interval). As a result of screening studies, 20 animals for inclusion in the experiment were identified, which were divided into two parity groups. The second group received L-ornithine L-aspartate as hepatotropic therapy at a dosage of 0.05 g/kg of body weight orally (in the form of a powder, previously dissolved in water) once a day for 28 days.Results. On the 7th day of the experiment, the GGT level decreased by an average of 5.63% compared to the control, on the 14th day — by 12.45%, on the 21st day — by 15.95%, at the end of the experiment — by 20.09%. Beginning on day 14 of therapy the amount of GGT in the experimental group reached reference values.Clinical trial data support l the thesis that LOLA has hepatoprotective properties in cases of hepatopathy of various origins, which is proved by a decrease in the level of GGT in the blood serum. Larger studies with a variety of designs, as well as comparison with other organ-specific measures, are needed to confirm these initial results. Thus, the use of LOLA hepatotropic therapy in liver diseases receives a new justification for use in veterinary medicine.