--- title: "L-Citrulline: Research & Side Effects | BodyHackGuide" url: https://www.bodyhackguide.co/compound/l-citrulline description: "L-Citrulline: mechanism, clinical studies & side effects." lang: en --- Skip to content Compare notes on r/BodyHackGuide (https://reddit.com/r/bodyhackguide) Compare notes with other researchers. Join r/BodyHackGuide (https://reddit.com/r/bodyhackguide) # L-Citrulline Performance: https://www.bodyhackguide.co/wiki#cat-performance Status Phase 3,, not approved for human use Evidence Small human trials, graded on the Nootropic Pre-Workout Stack (https://www.bodyhackguide.co/stack/nootropic-pre-workout) L-citrulline is a non-protein amino acid, found in high concentrations in watermelon, that the small intestine makes and the kidneys convert into arginine, the amino acid the body uses to make nitric oxide. Reviewed 28 October 2026 01 Overview ## What L-Citrulline is L-citrulline is used as a dietary supplement, alone or as citrulline malate (L-citrulline combined with malic acid), and in a 20-person dose study it raised blood arginine more than arginine itself did (PMID: 31977835; PMID: 17662090). Pooled analyses of human trials found a small gain in strength and power output (PMID: 30895562) and a fall of about 4 mmHg in systolic blood pressure (PMID: 30788274), but no significant gain in endurance performance (PMID: 36079738; PMID: 37155582). An intravenous form tested in a 189-child phase 3 trial during heart surgery showed no significant difference from placebo on its primary endpoint (ClinicalTrials.gov NCT02891837). ### How it works ### Where citrulline comes from Citrulline is not used to build proteins (PMID: 17513438). In mammals, three enzymes control free citrulline: nitric oxide synthase (NOS) and ornithine carbamoyltransferase make it, and argininosuccinate synthetase converts it into argininosuccinate, the step before arginine (PMID: 16082501). The small intestine makes citrulline and releases it into the blood, the liver does not take it up, and the kidneys take up most of it and convert it into arginine, a route a 2005 review described as a masked form of arginine that avoids the liver (PMID: 16082501; PMID: 17513438). Plasma citrulline is used as a marker of intestinal function: in a 2018 meta-analysis it correlated with remaining small bowel length in short bowel syndrome (r = 0.67) (PMID: 29511548). Watermelon accumulates citrulline to very high levels, and industrial citrulline is made with optimized microbial strains (PMID: 28741223). Read the full mechanism Show less ### Why researchers give citrulline instead of arginine Oral arginine is extensively broken down before it reaches the circulation, by the enzyme arginase in the intestine, while citrulline is readily absorbed (PMID: 17662090). In a double-blind crossover study of 20 healthy volunteers, citrulline raised plasma arginine more effectively than arginine itself (PMID: 17662090). The highest regimen in that study (3 g twice a day for a week) raised the ratio of arginine to ADMA (asymmetric dimethylarginine, an internal inhibitor of nitric oxide synthase) from 186 to 278, urinary nitrate from 92 to 125 micromol per mmol creatinine, and urinary cyclic GMP (cGMP, the messenger nitric oxide works through) from 38 to 50 nmol per mmol creatinine (PMID: 17662090). No regimen in that study improved flow-mediated dilation (FMD, a measure of how well an artery widens) over baseline (PMID: 17662090). In 8 healthy men given single doses of 2 to 15 g, only plasma citrulline, ornithine and arginine changed among amino acids, arginine peaked 1.2 to 2.3 hours after the dose, and less than 5 percent of the citrulline appeared in urine; at the highest doses arginine rose less than expected, which the authors suggested may reflect saturation of conversion in the kidney (PMID: 17953788). ### From arginine to nitric oxide Nitric oxide synthase enzymes make nitric oxide from arginine, with citrulline as a by-product; nitric oxide then raises cGMP, which relaxes smooth muscle in vessels and airways, and the enzyme phosphodiesterase 5 (PDE5) breaks cGMP down (PMID: 25043200). A 2017 review found clear evidence that a single dose of citrulline raises plasma arginine, but inconsistent evidence that a single dose raises nitric oxide production or widens vessels (PMID: 27749691). The same review reported that regular use over weeks raised nitric oxide synthesis and lowered blood pressure in adults with prehypertension or hypertension, but not in people with normal blood pressure (PMID: 27749691). A 2020 review called the evidence for short-term gains in vessel widening and muscle blood flow scarce and inconsistent (PMID: 31977835). In a 2019 crossover trial in 27 men, resting plasma nitrate and nitrite measured 15.3 micromol/L after 8 g of citrulline malate and 13.4 after placebo, against 233.2 after beetroot juice (PMID: 31343548). ### Citrulline malate PubChem lists citrulline malate as L-citrulline combined with malic acid (CID 162762, C10H19N3O8, 309.27 g/mol). Malate is an intermediate of the cell's main energy cycle, the tricarboxylic acid cycle (PMID: 12145119). In 18 men who reported fatigue, 15 days of citrulline malate raised the rate of oxidative ATP production during finger exercise by 34 percent and sped phosphocreatine recovery by 20 percent on phosphorus magnetic resonance spectroscopy; the abstract describes measurements before, during and after treatment with no placebo group, and the authors proposed that extra malate fed the energy cycle (PMID: 12145119). A 1991 French study in people and animals described citrulline malate, under the name Stimol, as an anti-fatigue compound that stimulated urea production in the liver and bicarbonate reabsorption in the kidney (PMID: 1930358). In mice, citrulline lowered the rise in blood ammonia during exhausting swimming and lengthened swimming time (PMID: 21908948). ### Muscle protein In 8 healthy adults on a low-protein diet for 3 days, citrulline raised the synthesis rate of mixed muscle protein compared with a mix of nonessential amino acids (0.060 versus 0.049, P=0.03) (PMID: 24972455). Much of this protein research involves the Paris Descartes University nutrition laboratory of Luc Cynober and Christophe Moinard; the 8-person study was run with the Mayo Clinic (PMID: 17513438; PMID: 24972455; PMID: 29503060). ### Studied for - Sports nutrition - Exercise physiology - Vascular biology - Hypertension - Amino acid metabolism - Pediatric cardiac surgery - Urea cycle disorders ### Benefits listed - Small gain in strength and power output (meta-analysis of 12 studies, 198 participants) - About 3 more repetitions to failure after a single dose of citrulline malate (meta-analysis of 8 studies, 137 participants) - Lower systolic blood pressure, by about 4 mmHg, in a pooled analysis of 8 small trials - Lower aortic blood pressure in small trials of postmenopausal women with hypertension Show 4 more Show less - Higher plasma arginine, urinary nitrate and urinary cGMP in a 20-person dose study - Higher brachial artery flow-mediated dilation than placebo in a pooled analysis of 2 trials lasting 1 to 2 weeks - Lower perceived exertion and 24-hour muscle soreness after exercise (meta-analysis of 13 studies) - Improved erection hardness score in 12 of 24 men with mild erectile dysfunction (single-blind pilot study) 02 Research Free with email ## What the research shows ### Graded on a research bench Reference pages that put L-Citrulline next to the compounds people pair it with: roles, evidence, overlap and conflicts. No dosing. Research use only. - Nootropic Pre-Workout Stack Small human trials human data on 7 of 7 compounds on the bench: https://www.bodyhackguide.co/stack/nootropic-pre-workout ### Unlock the research summary Enter your email to keep reading. It is free, and it opens these sections on every compound page in this browser. - A summary of the key research - Safety and side effects - A link to the PubMed results You also get the free peptide cheat sheet by email. Unsubscribe anytime. Have an account? Sign in (https://www.bodyhackguide.co/auth) 03 Safety ## L-Citrulline side effects and interactions ### Side effects #### Common - Stomach discomfort after a single 8 g dose of citrulline malate (6 of 41 men in one trial) - Minor laboratory changes in lactate dehydrogenase and plasma amino acids in a 4-week tolerance study in healthy men that went up to 24 g a day (PMID: 36571619) #### Serious events - Serious adverse events in 11 of 99 children on intravenous citrulline and 6 of 90 on placebo during heart surgery (phase 3 trial, NCT02891837) ### Who should not use it Contraindications No drug label exists for L-citrulline, so no formal contraindications have been set. Cautions in the literature: - Blood pressure medicines and low blood pressure: L-citrulline lowered systolic blood pressure by about 4 mmHg in a pooled analysis of small trials (PMID: 30788274), and a 2018 review called for studies of L-citrulline taken with drugs for hypertension and cardiovascular disease (PMID: 30029482). - PDE5 inhibitors: L-citrulline raised urinary cGMP in healthy volunteers (PMID: 17662090), the messenger whose breakdown by PDE5 these drugs block (PMID: 25043200); PubMed lists no study of the combination's effect on blood pressure. - Pregnancy: a 2025 meta-analysis found only one L-citrulline trial in pregnancy, in 36 women, which reported no effect on pre-eclampsia or blood pressure (PMID: 39800868). - Long-term use: most citrulline trials lasted weeks, and a 2018 review stated that the safety and efficacy of long-term supplementation need further study (PMID: 30029482). - Inherited urea cycle disorders: citrulline is part of specialist treatment for some of these disorders, and the choice between citrulline and arginine depends on the missing enzyme (PMID: 16082501; PMID: 37480106). ### Interactions 2 pairings in our record: 1 with a caution and 1 to monitor. - PDE5 inhibitors (sildenafil, tadalafil) Caution L-citrulline raised urinary cGMP in healthy volunteers (PMID: 17662090), the messenger whose breakdown by PDE5 these drugs block (PMID: 25043200); PubMed lists no study of the combination's effect on blood pressure. - Blood pressure medicines Monitor L-citrulline lowered systolic blood pressure by about 4 mmHg in a pooled analysis of small trials (PMID: 30788274), and a 2018 review called for studies of L-citrulline taken with drugs for hypertension (PMID: 30029482). This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds. Need bloodwork before starting? Full hormone + metabolic panels from Anabolic Insights. Code CHONCH for first-order discount. Order Bloodwork (https://anabolicinsights.ai/?ref=nwm2zjb) 04 Dosing Free with email ## Dosing No dose on record Our record lists no dose for L-Citrulline. This section holds what it does list. ### Unlock the Dosing section - Route 05 Prices ## L-Citrulline prices No listings We do not track a vendor for L-Citrulline yet, so this page states no price. 06 Chemistry ## Chemistry and structure Molecular formula C6H13N3O3 Molecular mass 175.19 g/mol CAS number 372-75-8 Half-life No adult value found in PubMed abstracts; an estimated half-life of about 60 minutes after intravenous doses in 17 infants and children having heart surgery (PMID: 17662768) and about 16 minutes after a single oral dose in 10 premature newborns (PMID: 36316628). In healthy men given oral L-citrulline, plasma arginine peaked 1.2 to 2.3 hours after the dose (PMID: 17953788). View on PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/9750) 07 Related ## Related to L-Citrulline ### In the same category - ACE-031Phase 2 ACE-031 (international nonproprietary name ramatercept) is a dimeric fusion protein that joins the extracellular domain of human activin receptor type IIB to the Fc region of human IgG1, developed by Acceleron Pharma as a decoy receptor that traps myostatin and related growth factors before they can suppress muscle growth.: https://www.bodyhackguide.co/compound/ace-031 - ITPPPreclinical ITPP (myo-inositol trispyrophosphate, sometimes written myo-inositol tripyrophosphate or OXY111A in NormOxys trial documents) is a small-molecule allosteric effector of hemoglobin designed to increase the amount of oxygen red blood cells release to tissues.: https://www.bodyhackguide.co/compound/itpp - LGD-4033 (Ligandrol)Phase 2 LGD-4033, usually sold as ligandrol, is a nonsteroidal selective androgen receptor modulator that Viking Therapeutics took into clinical development under the code VK5211 (NCT02578095).: https://www.bodyhackguide.co/compound/lgd-4033 - Ostarine (Enobosarm, MK-2866)Phase 3 Ostarine is the market name for enobosarm, a nonsteroidal selective androgen receptor modulator first developed by GTx Inc under the codes GTx-024, MK-2866 and S-22.: https://www.bodyhackguide.co/compound/ostarine - PEG-MGFPreclinical PEG-MGF (Pegylated Mechano Growth Factor) is a synthetic, PEGylated form of Mechano Growth Factor (MGF) — an alternatively spliced variant of IGF-1 produced locally in muscle and other tissues in response to mechanical loading or damage.: https://www.bodyhackguide.co/compound/peg-mgf - RAD-140 (Testolone)Phase 1 RAD-140, sold as testolone and given the international nonproprietary name vosilasarm, is a nonsteroidal selective androgen receptor modulator developed at Radius Health, whose scientists reported the first-in-human trial, and first described in the medicinal chemistry literature as a compound with an oxadiazole core designed for oral androgen receptor activity with tissue selectivity.: https://www.bodyhackguide.co/compound/rad-140 All compounds (https://www.bodyhackguide.co/wiki) ### Compare L-Citrulline - Alternatives to L-Citrulline: https://www.bodyhackguide.co/alternatives-to/l-citrulline ### Research tools - Peptide Calculator Reconstitution and syringe units: https://www.bodyhackguide.co/tools/reconstitution - Reconstitution Guide How to mix, step by step: https://www.bodyhackguide.co/guides/how-to-reconstitute-peptides - Nasal Spray Calc mL per actuation: https://www.bodyhackguide.co/tools/intranasal - Half-Life Visualizer Decay curves: https://www.bodyhackguide.co/tools/halflife All articles (https://www.bodyhackguide.co/blog) 08 Questions ## Frequently asked questions What is L-citrulline? L-citrulline is an amino acid that the body does not use to build proteins; the small intestine makes L-citrulline and the kidneys convert most of it into arginine (PMID: 16082501; PMID: 17513438). L-citrulline is found in high concentrations in watermelon (PMID: 30029482). What is the difference between L-citrulline and citrulline malate? Citrulline malate is L-citrulline combined with malic acid, and PubChem lists citrulline malate as its own compound (CID 162762) with a molecular weight of 309.27 g/mol, against 175.19 g/mol for L-citrulline (CID 9750). In a 2021 meta-analysis of 8 trials, citrulline malate, the malic acid form of L-citrulline, led to about 3 more repetitions to failure than placebo (PMID: 34010809). The pooled blood pressure analyses studied L-citrulline supplements (PMID: 30788274), and a 2025 analysis of L-citrulline also included watermelon products and trials that combined L-citrulline with L-arginine (PMID: 40789388). Does L-citrulline improve exercise performance? A 2019 meta-analysis of 12 studies found that L-citrulline or citrulline malate gave a small gain in strength and power output, though the confidence interval of every single study crossed zero (PMID: 30895562). Meta-analyses found no benefit of L-citrulline on endurance performance (PMID: 36079738; PMID: 37155582). Individual L-citrulline trials disagree: one found a faster cycling time trial in 22 trained men (PMID: 26900386), and another found a slightly shorter treadmill time to exhaustion in 17 adults (PMID: 16679980). Does L-citrulline lower blood pressure? A 2019 pooled analysis of 8 small L-citrulline trials found a fall of 4.1 mmHg in systolic blood pressure and no significant change in diastolic pressure (PMID: 30788274). Another pooled analysis of 5 L-citrulline interventions found no significant effect (PMID: 30284051). Many L-citrulline blood pressure trials come from one research group, led by Arturo Figueroa (PMID: 27749691; PMID: 36297080). A 2018 meta-analysis that reported a larger 7.5 mmHg fall with L-citrulline was retracted (PMID: 30206378; PMID: 31690817). Does L-citrulline raise nitric oxide? In 20 healthy volunteers, a week of L-citrulline raised plasma arginine and urinary nitrate and cGMP, markers of nitric oxide signaling, but did not improve flow-mediated dilation of the brachial artery (PMID: 17662090). A 2017 review found that single doses of L-citrulline raise plasma arginine reliably but nitric oxide production and vessel widening inconsistently (PMID: 27749691). In a 2019 trial, plasma nitrate and nitrite after an 8 g dose of citrulline malate, the malic acid form of L-citrulline, were close to placebo values and far below those after beetroot juice (PMID: 31343548). Is L-citrulline an approved drug? Drugs@FDA lists no approved drug with L-citrulline as an active ingredient (openFDA search, 25 October 2026). L-citrulline is used as a dietary supplement, a category whose definition includes amino acids and which the FDA does not approve before marketing (PMID: 30895562; FDA, Questions and Answers on Dietary Supplements). An intravenous form of L-citrulline reached phase 3 trials in children having heart surgery, where it did not differ significantly from placebo on the primary endpoint (ClinicalTrials.gov NCT02891837). What side effects has L-citrulline shown in trials? Single L-citrulline doses of 2 to 15 g caused no side effects in 8 healthy men (PMID: 17953788), and a study in Japan of up to 24 g of L-citrulline a day for 4 weeks found no treatment-related adverse events (PMID: 36571619). Stomach discomfort followed a single 8 g dose of citrulline malate, the malic acid form of L-citrulline, in 6 of 41 men (PMID: 20386132). Free 2026 Peptide Cheat Sheet (PDF) 38 compounds and blends: vial sizes, BAC water volumes, dosing ranges and bloodwork markers. Download Free (https://www.bodyhackguide.co/guides/peptide-cheat-sheet-download) BodyHackGuide (https://www.bodyhackguide.co/) Your biohacking research hub: compound pricing, brain health protocols, dosing tools, and vendor reviews. support@bodyhackguide.co Join our Discord: https://discord.gg/Mhq5UdRYBA r/BodyHackGuide on Reddit: https://reddit.com/r/BodyHackGuide **Affiliate Disclosure:** We rank every vendor on the same public, reproducible methodology (https://www.bodyhackguide.co/vendors/methodology). Full details in our affiliate disclosure (https://www.bodyhackguide.co/affiliate-disclosure). **Research Disclaimer:** All compounds listed are for laboratory and research purposes only. Not for human consumption. This site does not sell or ship any products. Always consult a qualified healthcare professional and comply with local regulations. © 2026 BodyHackGuide. All rights reserved. - Terms: https://www.bodyhackguide.co/terms - Privacy: https://www.bodyhackguide.co/privacy ## Structured data ```json [ { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://www.bodyhackguide.co/" }, { "@type": "ListItem", "position": 2, "name": "Compounds", "item": "https://www.bodyhackguide.co/compare" }, { "@type": "ListItem", "position": 3, "name": "L-Citrulline" } ] }, { "@context": "https://schema.org", "@type": "MedicalWebPage", "name": "L-Citrulline", "description": "L-citrulline is a non-protein amino acid, found in high concentrations in watermelon, that the small intestine makes and the kidneys convert into arginine, the amino acid the body uses to make nitric oxide (PMID: 16082501; PMID: 17513438; PMID: 30029482). L-citrulline is used as a dietary supplement, alone or as citrulline malate (L-citrulline combined with malic acid), and in a 20-person dose study it raised blood arginine more than arginine itself did (PMID: 31977835; PMID: 17662090). Pooled analyses of human trials found a small gain in strength and power output (PMID: 30895562) and a fall of about 4 mmHg in systolic blood pressure (PMID: 30788274), but no significant gain in endurance performance (PMID: 36079738; PMID: 37155582). An intravenous form tested in a 189-child phase 3 trial during heart surgery showed no significant difference from placebo on its primary endpoint (ClinicalTrials.gov NCT02891837).", "lastReviewed": "2026-10-28T15:43:02.303Z", "url": "https://www.bodyhackguide.co/compound/l-citrulline", "author": { "@type": "Person", "name": "BioChonch", "url": "https://www.bodyhackguide.co/about", "jobTitle": "Founder & Lead Researcher", "sameAs": [ "https://reddit.com/r/BodyHackGuide", "https://reddit.com/r/BrainHackGuide", "https://reddit.com/r/Biohackingher" ], "worksFor": { "@type": "Organization", "name": "BodyHackGuide", "url": "https://www.bodyhackguide.co" } }, "reviewedBy": { "@type": "Person", "name": "BioChonch", "url": "https://www.bodyhackguide.co/about", "jobTitle": "Founder & Lead Researcher", "sameAs": [ "https://reddit.com/r/BodyHackGuide", "https://reddit.com/r/BrainHackGuide", "https://reddit.com/r/Biohackingher" ], "worksFor": { "@type": "Organization", "name": "BodyHackGuide", "url": "https://www.bodyhackguide.co" } }, "publisher": { "@type": "Organization", "name": "BodyHackGuide", "url": "https://www.bodyhackguide.co" }, "mainContentOfPage": { "@type": "WebPageElement", "cssSelector": "main" }, "about": { "@type": "Drug", "name": "L-Citrulline", "alternateName": [ "Citrulline", "Citrulline malate", "L-citrulline malate", "Cit", "(2S)-2-amino-5-(carbamoylamino)pentanoic acid" ], "description": "L-citrulline is a non-protein amino acid, found in high concentrations in watermelon, that the small intestine makes and the kidneys convert into arginine, the amino acid the body uses to make nitric oxide (PMID: 16082501; PMID: 17513438; PMID: 30029482). L-citrulline is used as a dietary supplement, alone or as citrulline malate (L-citrulline combined with malic acid), and in a 20-person dose study it raised blood arginine more than arginine itself did (PMID: 31977835; PMID: 17662090). Pooled analyses of human trials found a small gain in strength and power output (PMID: 30895562) and a fall of about 4 mmHg in systolic blood pressure (PMID: 30788274), but no significant gain in endurance performance (PMID: 36079738; PMID: 37155582). An intravenous form tested in a 189-child phase 3 trial during heart surgery showed no significant difference from placebo on its primary endpoint (ClinicalTrials.gov NCT02891837).", "activeIngredient": "L-Citrulline", "administrationRoute": "Oral, Intravenous", "mechanismOfAction": "Where citrulline comes from Citrulline is not used to build proteins (PMID: 17513438). In mammals, three enzymes control free citrulline: nitric oxide synthase (NOS) and ornithine carbamoyltransferase make it, and argininosuccinate synthetase converts it into argininosuccinate, the step before arginine (PMID: 16082501). The small intestine makes citrulline and releases it into the blood, the liver does not take it up, and the kidneys take up most of it and convert it into arginine, a route a 2005 review described as a masked form of arginine that avoids the liver (PMID: 16082501; PMID: 17513438). Plasma citrulline is used as a marker of intestinal function: in a 2018 meta-analysis it correlated with remaining small bowel length in short bowel syndrome (r = 0.67) (PMID: 29511548). Watermelon accumulates citrulline to very high levels, and industrial citrulline is made with optimized microbial strains (PMID: 28741223). Why researchers give citrulline instead of arginine Oral arginine is extensively broken down before it reaches the circulation, by the enzyme arginase in the intestine, while citrulline is readily absorbed (PMID: 17662090). In a double-blind crossover study of 20 healthy volunteers, citrulline raised plasma arginine more effectively than arginine itself (PMID: 17662090). The highest regimen in that study (3 g twice a day for a week) raised the ratio of arginine to ADMA (asymmetric dimethylarginine, an internal inhibitor of nitric oxide synthase) from 186 to 278, urinary nitrate from 92 to 125 micromol per mmol creatinine, and urinary cyclic GMP (cGMP, the messenger nitric oxide works through) from 38 to 50 nmol per mmol creatinine (PMID: 17662090). No regimen in that study improved flow-mediated dilation (FMD, a measure of how well an artery widens) over baseline (PMID: 17662090). In 8 healthy men given single doses of 2 to 15 g, only plasma citrulline, ornithine and arginine changed among amino acids, arginine peaked 1.2 to 2.3 hours after the dose, and less than 5 percent of the citrulline appeared in urine; at the highest doses arginine rose less than expected, which the authors suggested may reflect saturation of conversion in the kidney (PMID: 17953788). From arginine to nitric oxide Nitric oxide synthase enzymes make nitric oxide from arginine, with citrulline as a by-product; nitric oxide then raises cGMP, which relaxes smooth muscle in vessels and airways, and the enzyme phosphodiesterase 5 (PDE5) breaks cGMP down (PMID: 25043200). A 2017 review found clear evidence that a single dose of citrulline raises plasma arginine, but inconsistent evidence that a single dose raises nitric oxide production or widens vessels (PMID: 27749691). The same review reported that regular use over weeks raised nitric oxide synthesis and lowered blood pressure in adults with prehypertension or hypertension, but not in people with normal blood pressure (PMID: 27749691). A 2020 review called the evidence for short-term gains in vessel widening and muscle blood flow scarce and inconsistent (PMID: 31977835). In a 2019 crossover trial in 27 men, resting plasma nitrate and nitrite measured 15.3 micromol/L after 8 g of citrulline malate and 13.4 after placebo, against 233.2 after beetroot juice (PMID: 31343548). Citrulline malate PubChem lists citrulline malate as L-citrulline combined with malic acid (CID 162762, C10H19N3O8, 309.27 g/mol). Malate is an intermediate of the cell's main energy cycle, the tricarboxylic acid cycle (PMID: 12145119). In 18 men who reported fatigue, 15 days of citrulline malate raised the rate of oxidative ATP production during finger exercise by 34 percent and sped phosphocreatine recovery by 20 percent on phosphorus magnetic resonance spectroscopy; the abstract describes measurements before, during and after treatment with no placebo group, and the authors proposed that extra malate fed the energy cycle (PMID: 12145119). A 1991 French study in people and animals described citrulline malate, under the name Stimol, as an anti-fatigue compound that stimulated urea production in the liver and bicarbonate reabsorption in the kidney (PMID: 1930358). In mice, citrulline lowered the rise in blood ammonia during exhausting swimming and lengthened swimming time (PMID: 21908948). Muscle protein In 8 healthy adults on a low-protein diet for 3 days, citrulline raised the synthesis rate of mixed muscle protein compared with a mix of nonessential amino acids (0.060 versus 0.049, P=0.03) (PMID: 24972455). Much of this protein research involves the Paris Descartes University nutrition laboratory of Luc Cynober and Christophe Moinard; the 8-person study was run with the Mayo Clinic (PMID: 17513438; PMID: 24972455; PMID: 29503060).", "legalStatus": "Not approved for human use (research chemical)", "warning": "For research purposes only. Not for human consumption." } }, { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type": "Question", "name": "What is L-citrulline?", "acceptedAnswer": { "@type": "Answer", "text": "L-citrulline is an amino acid that the body does not use to build proteins; the small intestine makes L-citrulline and the kidneys convert most of it into arginine (PMID: 16082501; PMID: 17513438). L-citrulline is found in high concentrations in watermelon (PMID: 30029482)." } }, { "@type": "Question", "name": "What is the difference between L-citrulline and citrulline malate?", "acceptedAnswer": { "@type": "Answer", "text": "Citrulline malate is L-citrulline combined with malic acid, and PubChem lists citrulline malate as its own compound (CID 162762) with a molecular weight of 309.27 g/mol, against 175.19 g/mol for L-citrulline (CID 9750). In a 2021 meta-analysis of 8 trials, citrulline malate, the malic acid form of L-citrulline, led to about 3 more repetitions to failure than placebo (PMID: 34010809). The pooled blood pressure analyses studied L-citrulline supplements (PMID: 30788274), and a 2025 analysis of L-citrulline also included watermelon products and trials that combined L-citrulline with L-arginine (PMID: 40789388)." } }, { "@type": "Question", "name": "Does L-citrulline improve exercise performance?", "acceptedAnswer": { "@type": "Answer", "text": "A 2019 meta-analysis of 12 studies found that L-citrulline or citrulline malate gave a small gain in strength and power output, though the confidence interval of every single study crossed zero (PMID: 30895562). Meta-analyses found no benefit of L-citrulline on endurance performance (PMID: 36079738; PMID: 37155582). Individual L-citrulline trials disagree: one found a faster cycling time trial in 22 trained men (PMID: 26900386), and another found a slightly shorter treadmill time to exhaustion in 17 adults (PMID: 16679980)." } }, { "@type": "Question", "name": "Does L-citrulline lower blood pressure?", "acceptedAnswer": { "@type": "Answer", "text": "A 2019 pooled analysis of 8 small L-citrulline trials found a fall of 4.1 mmHg in systolic blood pressure and no significant change in diastolic pressure (PMID: 30788274). Another pooled analysis of 5 L-citrulline interventions found no significant effect (PMID: 30284051). Many L-citrulline blood pressure trials come from one research group, led by Arturo Figueroa (PMID: 27749691; PMID: 36297080). A 2018 meta-analysis that reported a larger 7.5 mmHg fall with L-citrulline was retracted (PMID: 30206378; PMID: 31690817)." } }, { "@type": "Question", "name": "Does L-citrulline raise nitric oxide?", "acceptedAnswer": { "@type": "Answer", "text": "In 20 healthy volunteers, a week of L-citrulline raised plasma arginine and urinary nitrate and cGMP, markers of nitric oxide signaling, but did not improve flow-mediated dilation of the brachial artery (PMID: 17662090). A 2017 review found that single doses of L-citrulline raise plasma arginine reliably but nitric oxide production and vessel widening inconsistently (PMID: 27749691). In a 2019 trial, plasma nitrate and nitrite after an 8 g dose of citrulline malate, the malic acid form of L-citrulline, were close to placebo values and far below those after beetroot juice (PMID: 31343548)." } }, { "@type": "Question", "name": "Is L-citrulline an approved drug?", "acceptedAnswer": { "@type": "Answer", "text": "Drugs@FDA lists no approved drug with L-citrulline as an active ingredient (openFDA search, 25 October 2026). L-citrulline is used as a dietary supplement, a category whose definition includes amino acids and which the FDA does not approve before marketing (PMID: 30895562; FDA, Questions and Answers on Dietary Supplements). An intravenous form of L-citrulline reached phase 3 trials in children having heart surgery, where it did not differ significantly from placebo on the primary endpoint (ClinicalTrials.gov NCT02891837)." } }, { "@type": "Question", "name": "What side effects has L-citrulline shown in trials?", "acceptedAnswer": { "@type": "Answer", "text": "Single L-citrulline doses of 2 to 15 g caused no side effects in 8 healthy men (PMID: 17953788), and a study in Japan of up to 24 g of L-citrulline a day for 4 weeks found no treatment-related adverse events (PMID: 36571619). Stomach discomfort followed a single 8 g dose of citrulline malate, the malic acid form of L-citrulline, in 6 of 41 men (PMID: 20386132)." } } ] }, { "@context": "https://schema.org", "@type": "Organization", "@id": "https://www.bodyhackguide.co#organization", "name": "BodyHackGuide", "alternateName": "BHG", "url": "https://www.bodyhackguide.co", "logo": { "@type": "ImageObject", "url": "https://www.bodyhackguide.co/logo.png", "width": 512, "height": 512 }, "description": "Evidence-based research reference for peptides and nootropics. 273 compound profiles, interactive dosing calculators, vendor price comparisons, and trust-scored vendor reviews scored on a public, reproducible methodology applied to every vendor. 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