L-citrulline / Generic mfg. - LARVOL DELTA

Quantitative characterization of L-citrulline as a precursor of L-arginine in rats: pharmacokinetic basis for nitric oxide-mediated effects. (PubMed, Front Pharmacol) - "It also indicated that CIT elimination was predominantly mediated by conversion to ARG (Fmet = 0.999), resulting in greater systemic ARG exposure following oral CIT than following direct oral ARG administration. These findings provide a quantitative pharmacokinetic basis for the NO-mediated pharmacodynamic effects observed with both compounds and support the role of CIT as an effective oral precursor of ARG."

Journal • PK/PD data • Preclinical • NOS3

What a negative trial does not tell us: Bayesian reanalysis of the enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients randomized clinical trial. (PubMed, Clin Nutr ESPEN) - P=N/A | "This Bayesian reanalysis demonstrates that the IMMUNOCITRE trial was insufficiently powered to characterize the effect of L-citrulline on organ dysfunction. In this unselected cohort with low-to-moderate initial severity, the probability of achieving a large, clinically meaningful benefit remains limited. These findings do not support immediate clinical implementation. Future multicenter randomized controlled trial is highly warranted but should specifically target patients with higher baseline organ dysfunction and documented arginine deficiency."

Clinical • Journal • Critical care • Infectious Disease • Septic Shock

Endothelial-mitochondrial coupling in mitochondrial disease: A systematic review and quantitative synthesis of vascular, biochemical, and oxidative bioenergetic dysfunction. (PubMed, Ther Adv Rare Dis) - "Improvements in endothelial function and NO synthesis following l-arginine or l-citrulline supplementation are consistent with a role for impaired endothelial NO signaling in the vascular manifestations of mitochondrial disease. These findings highlight the vascular endothelium as a potential therapeutic target and underscore the need for future clinical intervention trials that use standardized vascular and bioenergetic endpoints."

Journal • Review • Cardiovascular • CNS Disorders • Metabolic Disorders

The Modulating Effects of Fruit and Fruit-Derived Interventions on Arterial Stiffness. (PubMed, Nutrients) - "Nevertheless, further research is warranted to understand whether fruit-based interventions can produce demonstrable changes in arterial stiffness among varying populations, and when such changes are observed, to elucidate the mechanisms underlying these effects. Thus, additional randomized controlled trials, especially with sufficient durations and adequate sample sizes to detect structural changes in the vascular system, are needed."

Journal • Review • Cardiovascular • Inflammation

Integrated metabolomics and proteomics revealed the comprehensive mechanism of Sijunzi decoction and its active components in improving multi-system dysfunction induced by spleen deficiency syndrome. (PubMed, J Ethnopharmacol) - "SJZDP, SJZD-OGS, and SJZD-SMC collaboratively contributed to the therapeutic efficacy of SJZD in alleviating SDS by restoring gastrointestinal function and hepatic metabolism (centered on amino acid and energy metabolism). This was achieved through the regulation of key metabolites (e.g., L-ornithine, L-citrulline, and fumaric acid) and key targets (Abcg8, Ctsk, Ciapin1, and Esr1), and activation of the ESR1/AMPK and LKB1/AMPK signaling pathways. This study comprehensively elucidated the potential mechanisms underlying SJZD's therapeutic effects on SDS and clarified the distinct contributions of its active components. It also provided a valuable reference for systematically exploring the material basis of TCM based on active components."

Journal • Gastrointestinal Disorder • Metabolic Disorders • CTSK • ER • STK11

A dual-molecular interface engineering strategy for highly efficient and stable perovskite solar cells. (PubMed, Mater Horiz) - "Herein, we propose a dual-molecular co-modification strategy composed of L-citrulline and L-malic acid (CM) to construct a multifunctional interfacial layer with a bridging effect...As a result, rigid devices achieve an impressive champion power conversion efficiency (PCE) of 26.25%, and unencapsulated devices retain 88.31% of their initial efficiency after 1800 h of storage in air. This study provides an effective dual-molecular interface engineering approach for constructing highly efficient and stable perovskite photovoltaic devices."

Journal

Consensus statements for diagnostic criteria and management of MELAS and stroke-like episodes (SSIEM 2026) - "Consensus defined MELAS as a clinical syndrome characterised by one or more stroke-like episodes occurring in the context of mitochondrial dysfunction due to a pathogenic mitochondrial DNA variant, most commonly m.3243A>G in MT-TL1. Terminology such as "MELAS-like" or "MELAS spectrum" was not supported. The panel concluded that commonly used metabolic therapies, including L-arginine, L-citrulline, taurine, coenzyme Q₁₀, and vitamin supplements, lack robust evidence of efficacy and should be prioritised for evaluation in controlled clinical trials."

Cardiovascular • CNS Disorders • Epilepsy • Inflammatory Arthritis • Metabolic Disorders

Pharmacokinetics, Amino Acid Responses, and Short-Term Tolerability of Intravenous and Oral L-Citrulline in Healthy Neonatal Holstein Calves. (PubMed, J Vet Pharmacol Ther) - "Both routes increased plasma arginine (max +159% IV; +122% PO) and ornithine (max +132% IV; +149% PO) with no clinically relevant adverse effects or laboratory abnormalities during short-term monitoring of clinical, hematological, biochemical, blood gas/electrolyte, and coagulation variables. These findings support further evaluation of L-citrulline as a nutritional and/or therapeutic supplement in neonatal calves."

Journal • PK/PD data • Hematological Disorders

Application of 13C MRS demonstrates carbohydrate feeding spares muscle but not liver glycogen utilisation during high-intensity interval exercise. (PubMed, Am J Physiol Endocrinol Metab) - "Following 24 h of standardised dietary intake, nine male cyclists completed 8 x 5-min intervals (1-min recovery), ingesting either placebo (PLA), 60 g maltodextrin (CHO) or 60 g maltodextrin plus caffeine, taurine, l-theanine, l-citrulline and citicoline (CHO+) in a randomised crossover design. These findings demonstrate preferential use of skeletal muscle glycogen during HIIT, which is attenuated under conditions of CHO feeding. This sparing effect is, however, not evident with the co-ingestion of a caffeine containing multi-ingredient blend, potentially due to an increased capacity to sustain higher power outputs resulting in greater glycogen utilisation."

Journal

Arbuscular mycorrhizal fungi reshape carbon-nitrogen balance and metabolism in nitrogen-limited escarole (Cichorium endivia L.). (PubMed, J Plant Physiol) - "This metabolic response led to the accumulation of bioactive compounds such as riboflavin, L-citrulline, sarcosine, cyclic pyranopterin monophosphate, and 5-hydroxy-L-tryptophan. Overall, these findings demonstrate that AMF enhance plant performance under nitrogen limitation not by increasing nitrogen content per se, but by optimizing nitrogen utilization and reshaping metabolic networks associated with C/N balance."

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L-citrulline treatment of nitric oxide deficiency in MELAS a phase I dose-finding and safety study. (PubMed, Mol Genet Metab) - "While no DLTs were observed, the increase of guanidino compounds with 30 g and 40 g of L-citrulline needs to be further interrogated with serial measurements in a future study to ensure safety of these doses and determine whether the increase is sustained long term. A randomized placebo-controlled trial will be required to evaluate the efficacy of L-citrulline in individuals with MELAS."

Journal • P1 data • Cardiovascular • CNS Disorders • Metabolic Disorders

Effects of Nutritional Supplements on Vascular Function: A Narrative Review. (PubMed, J Clin Med) - "This review examines nutritional supplements targeting nitric oxide biology (L-arginine/L-citrulline and citrulline derived from watermelon), polyphenol-rich foods and extracts (cocoa flavan-3-ols and grape polyphenols), mitochondrial redox balance (coenzyme Q10 and the mitochondria-targeted antioxidant MitoQ), endothelial glycocalyx-supporting formulations, olive-derived bioactive compounds, curcumin, and S-allyl cysteine. Overall, current evidence suggests that several nutritional supplements may improve surrogate markers of vascular function; however, evidence demonstrating reductions in major cardiovascular events or cardiovascular mortality remains limited. Future research should prioritize adequately powered randomized controlled trials with longer follow-up, standardized supplement formulations, and clinically meaningful cardiovascular outcomes to more clearly define the role of nutritional supplements in cardiovascular prevention."

Journal • Review • Cardiovascular • Inflammation

Circadian Disruption Promotes Epileptic Seizures via the Ruminococcus gnavus-Arginine-NOX4-Ferroptosis Axis. (PubMed, Brain Res Bull) - "Metabolomic analysis demonstrated that elevated R. gnavus suppressed the expression of argininosuccinate synthase 1 (ASS1), a key enzyme for arginine biosynthesis in the kidney, leading to impaired L-citrulline-to-L-arginine conversion and consequently decreased L-arginine levels in serum and hippocampal tissues...Importantly, L-arginine supplementation significantly prolonged seizure latency and reduced seizure frequency by reversing ferroptosis activation through downregulating NOX4-ACSL4 expression and upregulating GPX4 expression. This study unveils a complete signaling axis whereby CRD promotes epileptic seizures through the R. gnavus-ASS1-arginine-NOX4-ferroptosis cascade, providing novel therapeutic targets for clinical intervention."

Journal • CNS Disorders • Epilepsy • Sleep Disorder • Transplantation • ACSL4 • ASS1 • GPX4 • NOX4

L-citrulline as a nitric oxide-modulating therapeutic adjunct to exercise: effects on vascular function, arterial stiffness, and cardiometabolic health in postmenopausal and older women. (PubMed, Amino Acids) - "Findings from preclinical and clinical studies suggest that this combined intervention can reduce arterial stiffness, enhance leg muscle strength, increase lean body mass, and improve overall physical function, potentially via NO-mediated vasodilation, the mechanistic target of rapamycin signaling, improved mitochondrial function, and reduced oxidative stress. These effects are especially relevant in postmenopausal populations at risk for cardiovascular disease and sarcopenia. While early results are promising, further high-quality randomized controlled trials are needed to confirm these benefits, establish optimal dosing strategies, and determine long-term clinical relevance."

Journal • Review • Cardiovascular • Sarcopenia

Topical Trichosanthis Radix Water Extract Attenuates Atopic Dermatitis-Like Skin Inflammation: Marker Standardization, Network Pharmacology, and Preclinical Validation. (PubMed, Mediators Inflamm) - "Twenty-five overlapping genes formed a compact interaction module enriched for immune signaling and lipid/nuclear receptor-related pathways, and HPLC-ELSD detected and quantified L-citrulline as a marker compound for TR extract standardization...In HaCaT cells, TR attenuated cytokine-induced inflammatory effectors and phosphorylation of MEK/ERK and STAT1. These findings indicate that TR water extract mitigates AD-relevant inflammatory signaling while improving a barrier-associated outcome, supporting further constituent-resolved and mechanism-directed studies."

Journal • Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • IFNG • IL1B • NLRP3 • TNFA

EVIDENCE FOR THE USE OF BIOACTIVE COMPOUNDS TO TREAT CHILDHOOD OBESITY AND RELATED CARDIO-METABOLIC ALTERATIONS (ESPGHAN 2026) - "Results The position paper synthesizes the available evidence across six predefined categories of bioactive compounds: (A) non-prebiotic fibers, (B) prebiotic fibers, (C) probiotics, synbiotics, and postbiotics, (D) omega-3 fatty acids, (E) vitamin D, and (F) other bioactive compounds (including carnitine, curcumin, zinc, L-citrulline and phytosterols)...Conclusions The collected evidence will be synthesized through a network meta-analysis to delineate the comparative effectiveness and potential interrelationships among different bioactive compounds, thereby supporting informed, evidence-based use in the clinical management of childhood obesity. Contact e-mail address [email protected]"

Clinical • Genetic Disorders • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

L-Citrulline in Maternal-Fetal and Neonatal Health: Metabolic Mechanisms and Emerging Therapeutic Applications. (PubMed, Nutrients) - "This review provides a comprehensive evaluation of L-citrulline metabolism and its therapeutic potential from pregnancy through neonatal life, with emphasis on the intestinal-renal arginine-citrulline axis, endothelial function, and NO-mediated vascular regulation. We specifically examine the role of citrulline in key pathophysiologic mechanisms underlying maternal and neonatal disease, including endothelial dysfunction, impaired NO bioavailability, inflammation, oxidative stress, and abnormal placental vascular remodeling."

Journal • Review • Bronchopulmonary Dysplasia • Cardiovascular • Gastrointestinal Disorder • Gynecology • Hypertension • Infectious Disease • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Septic Shock

L-Citrulline: Novel Pharmacotherapy to Improve Outcomes in Infants and Children at Risk of Systemic or Pulmonary Vascular Disease. (PubMed, Pharmaceuticals (Basel)) - "This review will discuss the current status of the use of L-citrulline as a treatment to improve outcomes in pediatric patients suffering from disorders that place them at risk of developing systemic or pulmonary vascular disease. Future directions and the potential therapeutic use of L-citrulline in vascular diseases not yet under clinical investigation will also be discussed."

Journal • Review • Bronchopulmonary Dysplasia • Cardiovascular • Chronic Kidney Disease • Genetic Disorders • Heart Failure • Hematological Disorders • Hypertension • Nephrology • Pediatrics • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • Sickle Cell Disease

L-Arginine and Its Metabolites in Age-Related Cerebral Small Vessel Disease with Cognitive Impairment. (PubMed, Biomolecules) - "Levels of L-arginine and its metabolites-L-ornithine, L-citrulline, and asymmetric dimethylarginine (ADMA)-were measured; diffusion tensor MRI, MRI volumetry, and morphometry were performed...Patients with L-arginine ≥ 51.25 μmol/L demonstrated poorer performance on cognitive tests (Stroop test, trail-making test (TMT)-B, TMT B-A, 10-word test) and more severe brain damage, reflected by greater severity of MRI markers (white matter hyperintensities, microbleeds), changes in brain component volumes, cortical atrophy in specific regions, and impairment of white matter microstructural integrity. The obtained data indicate a pathogenetic link between disturbances in L-arginine homeostasis and the development of CSVD with CI and support the need for further studies aimed at refining approaches to their correction."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Vascular Neurology

Effect of a Daily Supplement on Plasma PAI-1 Levels (clinicaltrials.gov) - P1/2 | N=35 | Active, not recruiting | Sponsor: University of California, Los Angeles | Recruiting ➔ Active, not recruiting

Enrollment closed • FGF23

A molecular perspective on dimethylarginine dimethylaminohydrolases structure and function. (PubMed, Biochem J) - "Asymmetric dimethylarginine (ADMA) and monomethylarginine (L-NMMA) are endogenous NOS inhibitors whose accumulation leads to cardiovascular, renal, and neurodegenerative diseases. Dimethylarginine dimethylaminohydrolase (DDAH) converts ADMA and NMMA to L-citrulline and dimethylamine or monomethylamine, respectively, thereby controlling NO bioavailability...On the other hand, the assessment of DDAH2 function is still to be defined. The present review summarizes current molecular, biochemical, and structural insights into DDAH isoforms and discusses their potential as pharmacological targets for diseases associated with altered NO signaling."

Journal • Review • Cardiovascular • CNS Disorders • DDAH2

Effects of dietary L-Citrulline or L-arginine supplementation on immune function, intestinal morphology and intestinal microbiota in LPS-challenged broilers. (PubMed, Poult Sci) - "Notably, both L-Cit and L-Arg regulated the structure of the intestinal microbial community. L-Arg primarily promoted the abundance of beneficial bacteria such as g_Faecalibacterium and g_Barnesiella, whereas L-Cit significantly promoted g_Akkermansia to become the dominant genus and exert its function."

Journal • Inflammation • IL6 • TNFA

Recovery Yield and Defective Product Rate in a Bio-Based Amino Acid Crystallization Process. (PubMed, ACS Omega) - "This study presents a method for predicting the crystal purity and recovery yield of biobased amino acids, including l-alanine (ALA), l-histidine monohydrochloride monohydrate (HIS), and l-citrulline (CIT), in evaporative crystallization processes...Additionally, a quantitative analysis revealed that for all amino acids, the defective product rate decreases as the target crystal purity increases and minimum specification purity decreases. This study provides a basis for considering downstream recovery yield as an important metric in the design and evaluation of biobased processes involving crystallization."

Journal

Potential role of L-citrulline in regulating exercise performance and muscle protein metabolism. (PubMed, NPJ Sci Food) - "This review summarizes evidence from rodent and human studies, highlighting its effects on muscle function, protein synthesis, and underlying mechanisms. Key areas for future research include supplementation strategies, transport and metabolism pathways, mitochondrial function, and the interaction between L-Cit, gut microbiota, and muscle health, offering insights for nutritional interventions targeting aging and sarcopenia."

Journal • Review • Sarcopenia

Short-term administration of L-citrulline augments cardiac vagal control and reduces blood pressure in response to high-intensity exercise in untreated hypertensive males. (PubMed, Eur J Appl Physiol) - "PP was lower immediately post-exercise (p ≤ 0.005). Supplementation with L-citrulline for six days enhanced cardiovascular recovery after HIE by blunting surges in cardiac, and BP workload, and may assist in improving the clinical efficacy of HIE in hypertensive subjects."

Journal • Cardiovascular