L-citrulline / Generic mfg. - LARVOL DELTA

Computational Insights into the N-Migration and Oxidative Rearrangement Involved in the N-Nitrosourea Formation Catalyzed by the Cupin Domain of Multidomain Metalloenzyme SznF. (PubMed, J Chem Inf Model) - "The multidomain metalloenzyme SznF can specifically catalyze the conversion of Nω-methyl-l-arginine (l-NMA) to Nδ-hydroxy-Nω-methyl-Nω-nitroso-l-citrulline (l-NHMA), which is the key step for the biosynthesis of the N-nitrosourea pharmacophore, a precursor to the pancreatic cancer drug streptozotocin (SZN)...During the reaction, the iron ion plays important roles, not only as a central ion to coordinate with the substrate to mediate the H-abstraction, Fe-OOH attack as well as the bond cleavage and formation but also in stabilizing the NO radical and promoting the final N-N bond formation. These results may deepen the understanding of the catalysis of nonheme iron enzymes."

Journal • Oncology • Pancreatic Cancer • Solid Tumor

Effect of L-citrulline injection on testicular hemodynamics and semen quality in aged bucks. (PubMed, Vet Res Commun) - No abstract available

Journal

Chlorpyrifos induced dysregulation of arginine biosynthesis pathway aggravates Alzheimer's disease progression in 5XFAD mice via microbiota-gut-brain axis crosstalk. (PubMed, Environ Int) - "Therefore, disruption of this pathway in gut microbiota metabolites results in a significant decrease in L-Citrulline (L-Cit) concentration, thereby causing a marked reduction in serum L-Arginine (L-Arg) levels...L-Cit supplementation significantly increase serum L-Arg levels in CPF-exposed 5XFAD mice, thereby alleviating AD pathology and improving cognitive function. Collectively, these findings reveal a novel arginine metabolism-mediated mechanism along the microbiota-gut-brain axis in CPF-mediated AD pathogenesis and underscore the therapeutic potential of L-Cit for CPF-related neurodegenerative disorders."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • CCL3

Effects of Food Bioactive Compounds on Oxidative Stress and the Antioxidant Defense System in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Nutr Rev) - "Supplementation with food bioactive compounds such as vitamin E, vitamin D, curcumin, and ALA may help to regulate HbA1c levels and enhance antioxidant defenses in patients with T2DM, indicating significant clinical potential for diabetes management. However, further research is needed to confirm their clinical efficacy and to determine optimal dosing strategies."

Journal • Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Cardio-Renal Effects of Short-Term Fructose Treatment in Hypertensive Rats: Focused on NO/ROS Balance. (PubMed, Physiol Res) - "We assessed systolic blood pressure (tail-cuff), plasma lipid levels, tissue conjugated diene concentrations, protein expression of NADPH oxidase, NF-kappaB, and SOD (Western blot), and total NO synthase (NOS) activity ([3H]-L-arginine to [3H]-L-citrulline)...We can conclude that even moderate, short-term fructose intake induces strain-dependent dyslipidemia and an early shift of the renal redox milieu toward oxidative stress, accompanied by reduced NOS activity, while leaving blood pressure unchanged. The kidney appears more susceptible than the heart, particularly in the hypertensive background, highlighting the NO/ROS axis as an early target for intervention."

Journal • Preclinical • Dyslipidemia • Metabolic Disorders • NFKB1

Rationally engineered PEGylated l-citrulline functionalized baicalein encapsulated HSA nanopolymer guided by molecular docking for tumor microenvironment responsive and redox modulated colon cancer therapy. (PubMed, RSC Adv) - "Mechanistically, treatment induced elevated ROS levels, GSH depletion, mitochondrial depolarization, nuclear condensation, cytoskeletal collapse, and G0/G1 cell-cycle arrest. Furthermore, the formulation displayed potent antioxidant activity across DPPH, NO, SOD, and lipid peroxidation assays, with IC50 values approaching ascorbic acid, validating synergistic PEG-LC functionalization and HSA-mediated stabilization as a promising redox-driven nanoplatform for targeted colon cancer therapy."

Biomarker • Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CDC37

In vitro synthesis of β-aspartyl-basic amino acid dipeptides via a multi-enzyme cascade system with ATP regeneration. (PubMed, J Biotechnol) - "This enzyme enables both primer-independent polymerization of poly-L-Arg/L-Lys-poly(L-Asp) backbones and primer-dependent incorporation of non-canonical substrates (L-ornithine and L-citrulline), thereby expanding the repertoire of cyanophycin derivatives...This method achieved complete conversion of CGP into classical dipeptides β-Asp-Arg and β-Asp-Lys, with the highest titer reaching 80mM, while also generating non-classical products β-Asp-Orn and β-Asp-Cit. These results highlight the robustness and versatility of this strategy, offering a promising route for the scalable synthesis of β-Asp-basic amino acid dipeptides."

Journal • Preclinical

L-citrulline to Improve Adverse Outcomes in Admitted Children (EChiLiBRiST, Clinical Trial 2, Inpatients) (clinicaltrials.gov) - P=N/A | N=2200 | Recruiting | Sponsor: Barcelona Institute for Global Health | Not yet recruiting ➔ Recruiting | Trial completion date: Apr 2027 ➔ Aug 2027 | Trial primary completion date: Jan 2027 ➔ Jun 2027

Adverse events • Biomarker • Enrollment open • Trial completion date • Trial primary completion date • Infectious Disease • Pediatrics

Impact of High-Fat Diet on Biochemical Changes Following Experimental Myocardial Infarction. (PubMed, J Cell Mol Med) - "NOS activity was assessed via [3H]-l-citrulline production, while the expression of eNOS, iNOS, NFκB and TLR4 in cardiac tissue was analysed by Western blot...Conjugated dienes were elevated post-MI and further increased by HFD. These findings demonstrate that HFD exacerbates post-MI inflammation and oxidative stress, impairing nitric oxide signalling and promoting adverse cardiac remodelling."

Journal • Atherosclerosis • Cardiovascular • Genetic Disorders • Inflammation • Myocardial Infarction • Obesity • IL6 • NOS3 • TLR4 • TNFA

Separation of Epimers of a Cleavable ADC Drug Linker Using SLIM-Ion Mobility Mass Spectrometry. (PubMed, J Am Soc Mass Spectrom) - "For instance, L-citrulline can be cleaved by cathepsin B, while D-citrulline is not...Using this novel approach, citrulline-containing DL's, compounds A-D, were all baseline resolved with a single set of TWIMS parameters. This work underscores the critical role of high-resolution SLIM-IM-MS in resolving subtle structural differences in chiral ADC components, providing essential insights into their development and quality control."

Journal • Oncology • CTSB • CTSS

Effects of L-Citrulline Supplementation on Endothelial Function, Arterial Stiffness, and Blood Glucose Level in the Fasted and Acute Hyperglycemic States in Middle-Aged and Older Adults with Type 2 Diabetes. (PubMed, Nutrients) - "During acute hyperglycemia, CIT supplementation increased FMD and reduced femoral-ankle PWV, aortic systolic BP, and glucose levels compared to placebo (all p < 0.05). CIT supplementation is beneficial to improve vascular function and glucose levels during chronic and acute hyperglycemia in middle-aged and older adults with T2DM."

Clinical • Journal • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Thermal stability, aqueous solubility, and hydration properties of L-citrulline from density, viscosity, and acoustic measurements, supported by DFT and MD simulations. (PubMed, Food Res Int) - "Structural differences between L-citrulline and L-arginine show different hydration behavior and physicochemical properties, with L-citrulline exhibiting lower electrostrictive effects. These results improve understanding of L-citrulline hydration and provide insights for optimizing formulations in food, pharmaceutical, and sports nutrition supplements."

Journal

Effects of L-citrulline supplementation and watermelon intake on arterial stiffness and endothelial function in middle-aged and older adults: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Front Nutr) - "Future large-scale studies are needed to confirm the effects of watermelon on vascular function. https://www.crd.york.ac.uk/prospero/CRD420251052954."

Journal • Retrospective data • Review • Cardiovascular

L-Citrulline inhibits Th2 cell activation via PLAC8 mediated autophagy and L-Citrulline depletion to alleviate pediatric asthma. (PubMed, Int Immunopharmacol) - "Further, Our study revealed that L-Cit inhibited, NO, ROS and alleviated asthma symptoms through placenta specific 8(PLAC8) mediated autophagy and reprograms of L-Cit metabolism in Th2 cells. In conclusion, we propose that L-Cit represents a potential therapeutic candidate for young patients suffering from chronic asthma."

Journal • Allergy • Asthma • Immunology • Inflammation • Pediatrics • Pulmonary Disease • Respiratory Diseases • CD4 • PLAC8

Construction of a silver-doped carbon dots-based fluorescent probe for trace tartrazine analysis in foodstuffs. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "In this study, we report the synthesis of silver-doped yellow-green fluorescent carbon dots (Ag-YGCDs) using a facile solvothermal method with L-citrulline, phthalamide, and silver nitrate as precursors...The constructed method was then successfully applied in various food matrices, including cocktails, juices, energy drinks, hard candies, gummy candies, and chocolate confectioneries. The recovery rates ranged from 91.4 % to 120 %, with relative standard deviations between 1.1 % and 3.7 %, confirming the method's reliability and accuracy."

Journal

Characterization of the gut microbiota in patients with stage III colorectal cancer: A case-control study. (PubMed, Gene) - "Distinct gut microbiome profiles between healthy and CRC were observed. In particular, the findings showed a significant reduction in microbial diversity in stage III CRC. This study provides initial metagenomic data on Malian patients with CRC. It will be used to create a larger cohort to better understand the relationship between CRC and the gut microbiota in the Malian CRC population."

Journal • Colorectal Cancer • Oncology • Solid Tumor

A multi-omics approach exploring the gut-liver axis following combined radiation exposure and burn injury in a Sinclair minipig model. (PubMed, Sci Rep) - "Intestinal barrier disruption was indicated by decreasing circulating l-citrulline in CI which correlated inversely with intestinal-Fatty Acid Binding Protein...Liver RNA-seq revealed group-specific gene expression changes, with CI-altered pathways implicating immune responses and lipid metabolism, which were correlated with gut microbiota such as Bacteroidaceae and Lachnospiraceae. Taken together, we present a first-of-its kind large animal model of radiation combined injury to highlight the interplay between gut-liver axis disruptions and systemic injury responses."

Journal • Gastrointestinal Disorder • Hepatology • Liver Failure • Metabolic Disorders • Thermal Injury • IL1B • NLRP3

The impacts of L-citrulline and sildenafil on penile and testicular vascular perfusion pattern, advanced testicular analysis, steroids, and semen picture in normospermic dogs. (PubMed, Vet Res Commun) - "An elevation of nitric oxide and estradiol levels was observed (P = 0.01) form 1 h in L-Cit + S group compared to other groups, while testosterone levels were increased (P = 0.01) from 1 h but rapidly declined till reach a lowest value at 48 h compared to other groups. Addition of L-citrulline to sildenafil demonstrated a more efficiency in improvement of blood flow, hormonal profile, and semen quality than using sildenafil alone due to the action of L-Cit on nitric oxide."

Journal

Sex- and Dose-Dependent Effect of L-Citrulline on Body Weight and Food Intake in Obese Type 2 Diabetic Rats. (PubMed, Int J Endocrinol Metab) - "The Cit decreased body weight, food intake, and water consumption in obese T2D male and female rats. These effects were sex- and dose-dependent."

Journal • Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

The Emerging Role of Citrulline and Theanine in Health and Disease: A Comprehensive Review. (PubMed, Nutrients) - "Non-proteinogenic amino acids, such as L-citrulline and L-theanine, have garnered attention for their potential health benefits, including enhanced immunity, antioxidant activity, and cardiovascular support...This review emphasizes the need for cautious interpretation of their benefits, acknowledging that while promising, some effects, such as those on muscle protein synthesis, require further validation compared to established nutrients like branched-chain amino acids. By bridging mechanistic insights with translational challenges, this work aims to guide future research toward sustainable nutraceutical production."

Journal • Review • Cardiovascular • Immune Modulation • Immunology

Impact of L-citrulline on meat production and quality: A study on its effects on meat attributes and nutritional composition. (PubMed, Poult Sci) - "Overall, this study suggests that a diet supplemented with 0.75 % l-Cit (T2), which could be a promising amino acid without affecting meat quality or consumer preferences, may improve growth performance, meat quality, the lipid profile (blood plasma), and thermoregulation in broilers."

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L-citrulline and L-arginine improve reproductive performance in primiparous and multiparous cows via distinct shared metabolic pathways and pyrimidine metabolism. (PubMed, Front Vet Sci) - "Additionally, L-Arg and L-Cit synergistically influenced pyrimidine metabolism, regulating the production of N-myristoylphosphorylcholine, N-oleoyl-d-erythro-sphingosylphosphorylcholine, 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine, and 1-docosahexaenoyl- 2-stearoyl-sn-glycero-3-phosphocholine. This modulation resulted in increased NO, GSH-Px, T-AOC, and VEGF in multiparous cows, ultimately supporting early embryo implantation."

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Metagenome-assembled genomes reveal microbial signatures and metabolic pathways linked to coronary artery disease. (PubMed, mSystems) - "Metabolic pathway analysis revealed significant urea cycle and L-citrulline biosynthesis enrichment in CAD cases, with Alistipes and Coprococcus as key contributors...Additionally, the metagenome-assembled genome-based analysis revealed strain-resolved functional heterogeneity that shapes host-microbe interactions and may contribute to CAD pathophysiology. These findings provide novel insights into gut dysbiosis in CAD and highlight the potential of microbiome-targeted therapeutic strategies in precision medicine."

Journal • Cardiovascular • Coronary Artery Disease • Gastrointestinal Disorder • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders

Lysinuric protein intolerance: Unusual clinical manifestations in a compound heterozygote with a novel pathogenic variant. (PubMed, Biochem Biophys Rep) - "His diet was titrated to his meet his caloric and protein needs (with restriction) and supplementation with l-arginine, l-citrulline and l-lysine. The patient's hyperammonemia has since resolved and his glutamine has normalized. Molecular testing revealed two pathogenic variants in SLC7A7, confirming his diagnosis of lysinuric protein intolerance."

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L-citrulline protects testicular Sertoli cell function by mitigating DNA damage via the gut-testis axis of sheep fed a high-concentrate diet. (PubMed, NPJ Biofilms Microbiomes) - "Interestingly, the effect of HCD-induced aberrant Sertoli cells function can be rescued by supplementation with L-citrulline. Collectively, these findings highlight the therapeutic potential of L-citrulline in protecting male reproductive health under dietary stress conditions, particularly through its action on the gut-testis axis."

Journal • Infertility • Sexual Disorders • Transplantation