L-citrulline / Generic mfg. - LARVOL DELTA

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."

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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."

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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."

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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

Watermelon Nutritional Composition with a Focus on L-Citrulline and Its Cardioprotective Health Effects-A Narrative Review. (PubMed, Nutrients) - "The beneficial effects of oral L-citrulline ingestion through watermelon require additional evidence, but it has already been demonstrated that it does not undergo hepatic metabolism, instead being transported to the kidneys to participate in de novo L-arginine synthesis. The generation of endogenous NO then causes positive biochemical, hemodynamic, and vascular effects, remodeling the physio-pathological conditions of those adults that present risk factors for cardiovascular diseases."

Journal • Review • Atherosclerosis • Cardiovascular • Hypertension

Metabolic Characteristics of PGPR-Induced Growth Promotion in Alfalfa (Medicago sativa L.). (PubMed, Metabolites) - "The L-citrulline and L-arginine contents were significantly upregulated, thereby affecting nitrogen metabolism and ultimately promoting plant growth. In addition, different branches of the isoflavonoid biosynthesis pathway showed differential regulation, indicating their close relationship with plant growth promotion. This study provides a new perspective for a deeper understanding of the molecular mechanisms by which PGPR promotes plant growth and lays a theoretical foundation for the future development of PGPR-based agricultural biological agents."

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Structural and functional characterization of gut microbiota in dyslipidemic patients from high-altitude Tibetan pastoral areas. (PubMed, Front Nutr) - "Functional prediction revealed that pathways involved in glycolysis, starch degradation, and biosynthesis of L-methionine, L-arginine, L-lysine, L-citrulline, and L-threonine were significantly downregulated in dyslipidemic patients, whereas pathways for the biosynthesis of lipopolysaccharides, fatty acids, polyamines, and (Kdo)₂-lipid A were enriched...In contrast, the enriched functional pathways were significantly negatively correlated with TC but positively correlated with high-density lipoprotein cholesterol (HDL-C). These findings clarify the alterations in gut microbiota composition and function in plateau-dwelling dyslipidemic populations and their associations with blood lipid levels, suggesting potential microbial biomarkers for hyperlipidemia in plateau environments."

Journal • Dyslipidemia • Metabolic Disorders

Bacillus Subtilis LN077 as a Probiotic Feed Additive Improves Goat Growth, Immunity, and Rumen Health. (PubMed, Probiotics Antimicrob Proteins) - "Furthermore, we identified several microbially derived metabolites, including dihydroceramide, bufotenin, N8-acetylspermidine, N1-acetylspermine, spermidine, theophylline, 6-carboxy-5,6,7,8-tetrahydropterin, pentadecanal, N-alpha-acetyl-L-citrulline, and octopine, and we elucidated their potential relationships with growth performance and the rumen microbiota...These findings suggest that B. subtilis LN077 improves rumen fermentation, immune function, and growth performance by modulating the rumen microbiota and its metabolites. Its application may serve as a promising strategy to reduce antibiotic dependence in goat production."

Journal • IL6 • TNFA

Effects of Citrulline or Watermelon Supplementation on Body Composition: A Systematic Review and Dose-Response Meta-Analysis. (PubMed, Nutrients) - "CIT supplementation appears to have no overall effect on body composition. However, exploratory findings indicated potential benefits at higher doses or shorter durations. Rigorous trials controlling for dietary intake and training variables are needed to clarify its long-term effects."

Clinical • Journal • Retrospective data • Review

The relationship between watermelon consumption and sarcopenia in an elderly general population: findings from the Tianjin chronic low-grade systemic inflammation and health study. (PubMed, Front Nutr) - "As this was a cross-sectional study, the findings indicate associations rather than causality, and reverse causation cannot be ruled out. Bioactive compounds in watermelon, such as L-citrulline, may be associated with muscle protein synthesis, meriting confirmation in future longitudinal and interventional studies."

Journal • Inflammation • Sarcopenia

Dose-Response Effect of Watermelon Consumption on Ambulatory Blood Pressure in Adults with Elevated Blood Pressure: A Randomized Controlled Pilot Trial. (PubMed, Nutrients) - "Background/Objectives: Watermelon (Citrullus lanatus) is a natural dietary source of L-citrulline and L-arginine, the two amino acids involved in nitric oxide (NO) production and vasodilation...However, plasma L-arginine concentrations and L-arginine/ADMA ratios significantly increased in the WM groups compared to the control (p = 0.009) after adjusting for age, BMI, race, and gender in the statistical model. Overall, BP was not significantly different after two different doses of watermelon compared to control; however, improvements in NO synthesis pathway precursors (L-arginine, ADMA) suggest potential for dietary modulation to support endothelial function and BP regulation."

Biomarker • Clinical • Journal • Cardiovascular • Hypertension

L-citrulline, Arginase Activity, and Nitrate As Potential Nitric Oxide-Related Markers of Subclinical Atherosclerosis in Healthy Middle-Aged Non-smokers: A Cross-Sectional Study. (PubMed, Cureus) - "Furthermore, plasma NO3 - levels exhibited a negative association with PWV in drinkers (p = 0.001, β = -0.274) and a positive association in non-drinkers (p = 0.005, β = 0.241). In conclusion, L-citrulline, arginase activity, and plasma NO3 - are potential markers of early vascular changes within subgroups of healthy middle-aged adults and may serve as targets for preventive medical approaches using diet or supplementation."

Journal • Observational data • Atherosclerosis • Cardiovascular