Citrulline

amino acid

Citrulline is an alpha-amino acid that, while not used for protein synthesis, is a critical component of the urea cycle. This metabolic process converts excess ammonia—a toxic byproduct of protein metabolism—into urea for safe excretion. This detoxification is essential for maintaining physiological balance and preventing the buildup of metabolic waste. A significant function of citrulline is its efficient conversion into L-arginine within the kidneys. Arginine acts as a precursor for nitric oxide, a molecule that signals blood vessels to relax and dilate. This improved vasodilation enhances circulation, facilitating the delivery of oxygen and nutrients to active muscle tissues during and after physical exertion. Because of these effects, citrulline is commonly used to support athletic endurance, reduce muscle fatigue and soreness, and assist with recovery. It may also help support healthy blood pressure levels and overall cardiovascular function. While naturally present in some foods, it is a frequent addition to sports nutrition and vascular support formulas.

Natural sources
WatermelonCucumbersPumpkinsSquashBitter melon

Ingredient forms

No public comparison lists found.

Optimal Dosage
Minimum3000 mg
Maximum6000 mg
Safety & Toxicity
4 safety notes
  • Individuals with low blood pressure or those taking blood pressure-lowering medications should consult a healthcare professional before use, as Citrulline can further lower blood pressure.
  • Pregnant or breastfeeding women should seek medical advice prior to use due to insufficient safety data.
  • Individuals with kidney disease should use with caution and under medical supervision, as Citrulline is metabolized and excreted by the kidneys.
  • Discontinue use and consult a doctor if severe side effects occur.
Goals
Cardiovascular Support
Impact
High effect
Typical dose:1500–6000 mg

L-citrulline increases arginine availability and nitric oxide production. These effects support blood flow, endothelial function, and blood pressure regulation.

Focuses on
Blood PressureNitric Oxide SupportVessel DilationArterial StiffnessExercise Circulation
Most relevant for
Middle-aged and older adults, particularly postmenopausal women, looking to maintain healthy blood pressure and arterial flexibility.

Potential benefits

  • Blood Pressure Reduction.Pooled research indicates modest improvements in systolic and diastolic blood pressure, particularly in hypertensive populations.
  • Improved Vessel Dilation.It supports nitric oxide synthesis, which may enhance the ability of blood vessels to widen and improve overall blood flow.
  • Vascular Flexibility.Supplementation has been shown in some trials to reduce arterial stiffness, a marker of cardiovascular health, when used consistently.

Limitations

  • Variable Effectiveness.Improvements in vascular function are inconsistent across different groups; for example, some studies found blood flow benefits in older men but not older women.
  • Focus on Markers.Most evidence relates to surrogate measures like blood pressure or artery diameter rather than long-term prevention of major cardiovascular events.
  • Requirement for Stress.Certain blood pressure and flow benefits appear more pronounced during exercise or physical stress rather than during normal resting states.
Things to consider

Avoid use during pregnancy as clinical trials in preeclampsia found no benefit and reported potential increases in systolic blood pressure and liver enzymes. Observational studies have associated naturally high blood citrulline levels with increased cardiovascular risk.

Study evidence

33 studies

Citrulline may modestly improve blood pressure and blood-vessel function in some adults, but findings vary and prevention of cardiovascular disease is unproven. Benefits do not extend to every setting: research in preeclampsia found no clinical benefit and raised specific safety concerns.

View goal
Fitness
Impact
High effect
Typical dose:4000–8000 mg

Citrulline is more effective at increasing blood arginine levels than taking arginine itself due to better bioavailability. The resulting increase in nitric oxide (NO) widens blood vessels, which can improve endurance, increase the 'pump' during workouts, and facilitate faster recovery.

Focuses on
Muscle soreness reductionPerceived exertionNitric oxide productionFunctional muscle strengthTraining adaptation
Most relevant for
Individuals looking to manage post-workout muscle soreness or older adults seeking to improve strength gains from resistance training.

Potential benefits

  • Muscle soreness reduction.Meta-analyses indicate that citrulline can significantly reduce muscle soreness at 24 and 48 hours post-exercise, which may assist in faster recovery between sessions.
  • Lowered perceived exertion.Supplementation may reduce the rating of perceived exertion during physical activity, potentially making high-intensity workouts feel less taxing.
  • Age-related strength support.In older adults, particularly those with obesity or hypertension, combining citrulline with exercise has been shown to improve lean mass and functional leg strength.

Limitations

  • Inconsistent performance gains.Pooled research suggests that acute ingestion does not reliably improve endurance performance or maximal strength in young, healthy, and resistance-trained adults.
  • Preparation variability.Many studies showing benefits used citrulline malate; it is unclear if pure L-citrulline or watermelon-derived sources provide identical ergogenic effects.
  • Training status impact.Benefits may be more pronounced in untrained or older populations, as highly trained athletes often see no significant improvement in exercise performance.
Things to consider

Citrulline may attenuate the blood pressure response to exercise in normotensive men.

Study evidence

45 studies

Citrulline has mixed effects on fitness: it may improve some training responses and muscle function in selected populations, but benefits are not consistent. Pooled research finds no clear improvement in endurance performance or maximal strength in healthy, trained adults.

View goal
Heart Health
Impact
High effect
Typical dose:2000–6000 mg

Unlike Arginine, which is heavily metabolized by the liver, Citrulline bypasses this process and is converted to Arginine in the kidneys, making it a more bioavailable precursor for NO synthesis. This sustained increase in NO improves endothelial function and vasodilation.

Focuses on
Blood pressure regulationEndothelial functionNitric oxide productionVascular blood flowCold-weather blood pressure response
Most relevant for
Adults with prehypertension or impaired vascular function, including postmenopausal women and those with type 2 diabetes.

Potential benefits

  • Blood Pressure Reduction.Meta-analyses indicate that supplementation can lower both systolic and diastolic blood pressure, with more pronounced effects observed in individuals with elevated baseline levels.
  • Improved Vessel Dilation.Regular use may enhance flow-mediated dilation, helping arteries widen more effectively in response to blood flow, particularly in patients with coronary artery disease.
  • Cold Stress Attenuation.Evidence suggests citrulline can help mitigate the sharp increases in blood pressure and arterial stiffness typically induced by exposure to cold environments.

Limitations

  • Variable Acute Response.Single doses have frequently shown no significant effect on vessel function in healthy young adults, indicating that benefits may depend on longer-term intake.
  • Inconsistent Functional Changes.Research on arterial stiffness (pulse wave velocity) remains mixed, with some studies showing no improvement despite reductions in blood pressure.
  • Lack of Long-Term Outcome Data.While citrulline improves cardiovascular risk markers, there is currently no evidence that it reduces the actual incidence of heart attacks or strokes.
Things to consider

Observational research has linked higher natural circulating levels of citrulline with increased cardiovascular risk markers, though these findings reflect internal metabolism rather than a direct risk from supplementation.

Study evidence

39 studies

Citrulline may modestly improve blood pressure and blood-vessel function, particularly in people with elevated blood pressure or impaired circulation. Results are inconsistent across settings, and the available research does not establish that supplementation prevents heart attacks, strokes or other cardiovascular events.

View goal
Muscle Gain
Impact
High effect
Typical dose:3–8 g

Improved blood flow can lead to better performance and a more significant 'pump' during workouts. It may also aid in recovery by reducing delayed onset muscle soreness (DOMS).

Focuses on
Muscle protein synthesisTraining volumeLean mass maintenanceExercise enduranceMuscle recovery
Most relevant for
Older individuals or those with low protein intake looking to support muscle maintenance and training capacity.

Potential benefits

  • Muscle growth in older adults.Unconfirmed. Some research in frail or older adults suggests a potential increase in lean mass when paired with exercise, but these benefits are not reliably seen in healthy younger populations.
  • Protein synthesis stimulation.Unconfirmed. Small studies show citrulline may stimulate muscle protein synthesis during low-protein intake, though it is unproven if this leads to actual muscle gain in well-nourished individuals.
  • Increased training volume.Unconfirmed. By improving the number of repetitions possible during a workout, citrulline may indirectly support growth, but direct evidence of increased muscle size from this effect is lacking.

Limitations

  • Unreliable for muscle hypertrophy.Large-scale meta-analyses have found no consistent benefit for increasing fat-free mass, muscle thickness, or overall body composition in healthy, resistance-trained adults.
  • Population-specific evidence.Most studies showing positive effects on muscle mass were conducted in malnourished or elderly populations, making the results less applicable to healthy athletes.
  • Reliance on indirect markers.Many potential benefits are based on short-term exercise performance or blood flow markers, which do not always translate into long-term increases in muscle tissue.

Study evidence

15 studies

Citrulline has not shown a consistent overall benefit for muscle gain. Some research suggests benefits in older or nutritionally vulnerable adults and small improvements in exercise performance, but these findings do not establish greater muscle growth in healthy people who train.

View goal
Weight Gain
Impact
High effect
Typical dose:4–8 g

Citrulline is a precursor to Arginine and is more effective at increasing blood Arginine levels than supplementing with Arginine itself. This leads to increased nitric oxide (NO) production, which widens blood vessels. The resulting improvements in circulation can enhance the 'pump' during workouts, support endurance, and facilitate better recovery.

Focuses on
muscle mass preservationstrength supportrecovery maintenancenutrient deliverycirculatory health
Most relevant for
Individuals aiming to preserve muscle mass during recovery or aging rather than those seeking to significantly increase total body weight.

Potential benefits

  • Lean Tissue Maintenance.Unconfirmed. Studies in malnourished older adults and patients recovering from surgery suggest it may help maintain muscle tissue, but its effectiveness for increasing body weight in healthy individuals is unproven.
  • Exercise-Related Muscle Support.Unconfirmed. While it does not directly increase scale weight, supplementation has been linked to improved muscle strength when combined with exercise, which may support muscle quality.

Limitations

  • No General Weight Gain Effect.Meta-analyses of randomized controlled trials indicate that citrulline has no significant overall impact on total body weight, BMI, or lean mass in healthy adults.
  • Potential for Fat Reduction.Clinical research often shows that citrulline may contribute to a decrease in body fat percentage, which may counteract goals focused solely on increasing total mass.
  • Population Specific Findings.Evidence for muscle or weight preservation is largely restricted to clinical populations, such as surgical patients or the malnourished elderly, with little evidence for healthy adults.

Study evidence

8 studies

Citrulline is not established as a weight-gain supplement. The available pooled research finds no clear increase in body weight or lean mass overall, while favorable findings mainly concern selected older adults or reduced weight loss during recovery from surgery.

View goal
Energy
Impact
Situational effect
Typical dose:3000–8000 mg

L-Citrulline is converted to L-Arginine in the kidneys, leading to a more sustained increase in plasma arginine and nitric oxide levels. Enhanced blood flow delivers more oxygen and nutrients to working muscles while clearing metabolic byproducts like ammonia, thereby improving endurance and reducing muscle soreness.

Focuses on
Fatigue resistanceExercise enduranceMuscle staminaCycling performanceTraining volume
Most relevant for
Active individuals and athletes seeking to delay muscle fatigue and improve endurance during high-intensity training sessions.

Potential benefits

  • Strength Training Endurance.Meta-analyses indicate a small increase in the number of repetitions performed before failure during high-intensity resistance exercise.
  • Cycling Performance.Some trials show improved time-trial completion speeds and sustained power output in trained male cyclists.
  • Aerobic Energy Support.Unconfirmed. Small studies suggest it may enhance muscle energy production at the cellular level, though its impact on felt energy or overall performance remains uncertain.

Limitations

  • Inconsistent Ergogenic Effects.Numerous high-quality trials have found no significant benefit for peak power, sprinting, or time-to-exhaustion across various populations.
  • Lack of Daily Energy Data.Evidence is largely restricted to athletic performance and does not confirm benefits for everyday energy or general vitality.
  • Unestablished Fatigue Recovery.Consensus guidelines indicate that evidence is insufficient to prove that it speeds up the restoration of muscle function after exercise.
Things to consider

Mild stomach discomfort has been reported by a small number of participants at doses of 8 grams or higher.

Study evidence

14 studies

Citrulline may modestly improve performance in some exercise settings, but fatigue and recovery results are inconsistent. Most supplied research concerns exercise tests, often using citrulline malate, and does not establish that citrulline increases everyday energy or treats persistent fatigue.

View goal

Studies

Research connections will load here.
Interactions

Positive Interactions

Arginine
Citrulline is converted to Arginine in the body, boosting overall nitric oxide production when taken together, enhancing blood flow and performance.
Arginine Alpha Ketoglutarate
By increasing Arginine levels, Citrulline can augment the nitric oxide boosting effects of AAKG, further supporting vasodilation and muscle pumps.
Creatine
Citrulline's improved blood flow can enhance nutrient delivery to muscles, complementing Creatine's role in energy production and supporting overall exercise performance.
L-Carnitine
Citrulline's benefits in circulation can enhance the delivery of L-Carnitine to tissues, supporting its role in energy metabolism and fatty acid transport.
Acetyl L-Carnitine
Citrulline's improved blood flow can enhance the delivery of Acetyl L-Carnitine to target tissues, supporting its roles in cognitive function and energy metabolism.
Coenzyme Q-10
Both support cardiovascular health; Citrulline improves blood flow while CoQ10 provides antioxidant support and aids in cellular energy production, creating a synergistic effect.
Magnesium
Magnesium supports muscle function and relaxation, while Citrulline improves blood flow to muscles, potentially enhancing performance and recovery synergistically.
Vitamin C
Vitamin C is an antioxidant that can protect nitric oxide from degradation, potentially prolonging and enhancing the vasodilatory effects mediated by Citrulline.
Folate
Folate is involved in nitric oxide synthesis and metabolism, and adequate levels can support the pathway that Citrulline influences to produce NO.
Sources

Up to five highest-ranked published examples per goal. Study counts and charts include all published studies for the connection.

  1. Does l-citrulline supplementation and watermelon intake reduce blood pressure in middle-aged and older adults? A systematic review and meta-analysis of randomized controlled trials.
    Luo P; Chen J; Liu K; Zhang J · Clinical nutrition ESPEN · 2025
    Meta-analysis415 participants15 studies pooledCardiovascular Support
  2. Micronutrient Supplementation to Reduce Cardiovascular Risk.
    An P; Wan S; Luo Y; Luo J; Zhang X; Zhou S; Xu T; He J; Mechanick JI; Wu WC; Ren F; Liu S · Journal of the American College of Cardiology · 2022
    Meta-analysis883,627 participants884 studies pooledCardiovascular Support
  3. l-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans.
    Bailey SJ; Blackwell JR; Lord T; Vanhatalo A; Winyard PG; Jones AM · Journal of applied physiology (Bethesda, Md. : 1985) · 2016
    Randomized trial10 participantsCardiovascular Support
  4. Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women.
    Maharaj A; Fischer SM; Dillon KN; Kang Y; Martinez MA; Figueroa A · Nutrients · 2022
    Randomized trial25 participantsCardiovascular SupportHeart Health
  5. Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men.
    Ochiai M; Hayashi T; Morita M; Ina K; Maeda M; Watanabe F; Morishita K · International journal of cardiology · 2012
    Randomized trial15 participantsCardiovascular Support
  6. The Effects of Combined Exercise with Citrulline Supplementation on Body Composition and Lower Limb Function of Overweight Older Adults: A Systematic Review and Meta-Analysis.
    Xie S; Li S; Shaharudin S · Journal of sports science & medicine · 2023
    Meta-analysis303 participants7 studies pooledFitness
  7. Effect of High-Intensity Interval Training Combined with L-Citrulline Supplementation on Functional Capacities and Muscle Function in Dynapenic-Obese Older Adults.
    Buckinx F; Gouspillou G; Carvalho LP; Marcangeli V; El Hajj Boutros G; Dulac M; Noirez P; Morais JA; Gaudreau P; Aubertin-Leheudre M · Journal of clinical medicine · 2020
    Randomized trial56 participantsFitnessMuscle Gain
  8. Initial Dietary Protein Intake Influence Muscle Function Adaptations in Older Men and Women Following High-Intensity Interval Training Combined with Citrulline.
    Buckinx F; Marcangeli V; Pinheiro Carvalho L; Dulac M; Hajj Boutros G; Gouspillou G; Gaudreau P; Morais J; Noirez P; Aubertin-Leheudre M · Nutrients · 2020
    Randomized trial73 participantsFitness
  9. Effects of Citrulline alone or combined with exercise on muscle mass, muscle strength, and physical performance among older adults: a systematic review.
    Aubertin-Leheudre M; Buckinx F · Current opinion in clinical nutrition and metabolic care · 2021
    Systematic review250 participants6 studies pooledMuscle GainFitness
  10. Combined Vs. Single Supplementation of L-Citrulline and Sodium Bicarbonate During Sprint Interval Training in Basketball Players: Effects on Physical Performance and Hormonal Adaptations.
    Wang Y; Wang Y; Qian K · Journal of sports science & medicine · 2025
    Randomized trial40 participantsFitness
  11. Effect of oral L-citrulline on brachial and aortic blood pressure defined by resting status: evidence from randomized controlled trials.
    Yang HH; Li XL; Zhang WG; Figueroa A; Chen LH; Qin LQ · Nutrition & metabolism · 2022
    Meta-analysis8 studies pooledHeart Health
  12. Impact of L-Citrulline Supplementation and HIIT on Lipid Profile, Arterial Stiffness, and Fat Mass in Obese Adolescents with Metabolic-Dysfunction-Associated Fatty Liver Disease: A Randomized Clinical Trial.
    Rodríguez-Carrillo AA; Espinoza-Vargas MR; Vargas-Ortiz K; Ibarra-Reynoso LDR; Olvera-Juárez M; Gómez-Ojeda A; Garay-Sevilla ME; Figueroa A · Nutrients · 2025
    Randomized trial44 participantsHeart Health
  13. Vascular effects of l-citrulline supplementation in healthy adults are largely influenced by the prehypertensive range of blood pressure: A double-blind, randomized, placebo-controlled, parallel-group study.
    Nogimura D; Nagaoka K; Ogino K; Ogino N; Moriyasu K; Morita M · Nutrition research (New York, N.Y.) · 2026
    Randomized trial66 participantsHeart Health
  14. The Assessment of short-term effect of L-Citrulline on endothelial function via FMD to NMD ratio in known CAD patients: A randomized, cross-over clinical trial (Clinical trial number: NCT02638727).
    Safi M; Mahjoob MP; Nateghi S; Khaheshi I; Akbarzadeh MA; Naderian M · Romanian journal of internal medicine = Revue roumaine de medecine interne · 2017
    Randomized trial30 participantsHeart Health
  15. Impact of L-citrulline supplementation and whole-body vibration training on arterial stiffness and leg muscle function in obese postmenopausal women with high blood pressure.
    Figueroa A; Alvarez-Alvarado S; Ormsbee MJ; Madzima TA; Campbell JC; Wong A · Experimental gerontology · 2015
    Randomized trial41 participantsMuscle Gain
  16. Citrulline Supplementation Improves Microvascular Function and Muscle Strength in Middle-Aged and Older Adults with Type 2 Diabetes.
    Figueroa A; Dillon KN; Levitt DE; Kang Y · Nutrients · 2025
    Randomized trial16 participantsMuscle Gain
  17. Citrulline stimulates muscle protein synthesis in the post-absorptive state in healthy people fed a low-protein diet - A pilot study.
    Jourdan M; Nair KS; Carter RE; Schimke J; Ford GC; Marc J; Aussel C; Cynober L · Clinical nutrition (Edinburgh, Scotland) · 2016
    Randomized trial8 participantsMuscle Gain
  18. Effects of Citrulline Supplementation on Body Weight in Patients With Hepatobiliary Pancreatic Surgery.
    Yang JA; Lee KE; Park JH; Yee J; Kim JY; Gwak HS · Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2020
    Cohort study138 participantsWeight Gain
  19. Impact of high-intensity interval training with or without l-citrulline on physical performance, skeletal muscle, and adipose tissue in obese older adults.
    Marcangeli V; Youssef L; Dulac M; Carvalho LP; Hajj-Boutros G; Reynaud O; Guegan B; Buckinx F; Gaudreau P; Morais JA; Mauriège P; Noirez P; Aubertin-Leheudre M; Gouspillou G · Journal of cachexia, sarcopenia and muscle · 2022
    Clinical trial81 participantsWeight Gain
  20. Synergistic effect of long-term L-citruline supplementation combined with exercise on body composition in adults: A systematic review and meta-analysis of randomized controlled trials.
    Wang W; Cai S; Liu K; Luo P · Complementary therapies in medicine · 2026
    Meta-analysis9 studies pooledWeight Gain
  21. Effects of Citrulline or Watermelon Supplementation on Body Composition: A Systematic Review and Dose-Response Meta-Analysis.
    Ashtary-Larky D; Mohammadi S; Mousavi SAH; Hajizadeh L; Candow DG; Forbes SC; Afrisham R; Farrokhi V; Antonio J; Suzuki K · Nutrients · 2025
    Meta-analysis21 studies pooledWeight Gain
  22. Impact of 3-week citrulline supplementation on postprandial protein metabolism in malnourished older patients: The Ciproage randomized controlled trial.
    Bouillanne O; Melchior JC; Faure C; Paul M; Canouï-Poitrine F; Boirie Y; Chevenne D; Forasassi C; Guery E; Herbaud S; Le Corvoisier P; Neveux N; Nivet-Antoine V; Astier A; Raynaud-Simon A; Walrand S; Cynober L; Aussel C · Clinical nutrition (Edinburgh, Scotland) · 2020
    Randomized trial24 participantsWeight Gain
  23. Acute Effect of Citrulline Malate on Repetition Performance During Strength Training: A Systematic Review and Meta-Analysis.
    Vårvik FT; Bjørnsen T; Gonzalez AM · International journal of sport nutrition and exercise metabolism · 2021
    Meta-analysis137 participants8 studies pooledEnergy
  24. Oral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover study.
    Suzuki T; Morita M; Kobayashi Y; Kamimura A · Journal of the International Society of Sports Nutrition · 2016
    Randomized trial22 participantsEnergy
  25. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness.
    Pérez-Guisado J; Jakeman PM · Journal of strength and conditioning research · 2010
    Randomized trial41 participantsEnergy
  26. Citrulline/malate promotes aerobic energy production in human exercising muscle.
    Bendahan D; Mattei JP; Ghattas B; Confort-Gouny S; Le Guern ME; Cozzone PJ · British journal of sports medicine · 2002
    Single-arm trial18 participantsEnergy
  27. The Effect of Citrulline Malate Supplementation on Muscle Fatigue Among Healthy Participants.
    Farney TM; Bliss MV; Hearon CM; Salazar DA · Journal of strength and conditioning research · 2019
    Randomized trial12 participantsEnergy