Lci9.0

L-Citrulline Research

39 peer-reviewed studies · Evidence score: 9/10

L-Arginine and L-Citrulline for Prevention and Treatment of Pre-Eclampsia: A Systematic Review and Meta-Analysis

Makama M et al. • BJOG : an international journal of obstetrics and gynaecology (2025)

L-arginine may be promising for pre-eclampsia prevention and treatment, but findings should be interpreted cautiously.

In prevention trials, L-arginine was associated with a reduced risk of pre-eclampsia (relative risk [RR] 0.52; 95% confidence interval [CI], 0.35, 0.78; low-certainty evidence, four trials) and severe pre-eclampsia (RR 0.23; 95% CI, 0.09, 0.55; low-certainty evidence, three trials).
In treatment trials, L-arginine may reduce mean systolic blood pressure (MD -5.64 mmHg; 95% CI, -10.66, -0.62; very low-certainty evidence, three trials) and fetal growth restriction (RR 0.46; 95% CI, 0.26, 0.81; low-certainty evidence, two trials).
L-arginine may be promising for pre-eclampsia prevention and treatment, but findings should be interpreted cautiously.

Meta-Analysisn=2,028

DOI

Absence of Effects of L-Arginine and L-Citrulline on Inflammatory Biomarkers and Oxidative Stress in Response to Physical Exercise: A Systematic Review with Meta-Analysis

Porto AA et al. • Nutrients (2023)

In conclusion, our systematic review and meta-analysis found that L-Citrulline and L-Arginine did not influence inflammatory biomarkers and oxidative stress after exercise.

We observed no difference between pre- vs. post-exercise for oxidative stress (subtotal = -0.21 [CI: -0.56, 0.14], p = 0.24, and heterogeneity = 0%.
In the sub-group "L-Arginine" we found a subtotal = -0.29 [-0.71, 0.12], p = 0.16, and heterogeneity = 0%.
No differences were observed between groups (p = 0.47), and I² = 0%) or in antioxidant activity (subtotal = -0.28 [-1.65, 1.08], p = 0.68, and heterogeneity = 0%).

Meta-Analysisn=1,080

DOI

Micronutrient Supplementation to Reduce Cardiovascular Risk

An P et al. • Journal of the American College of Cardiology (2022)

Supplementation of some but not all micronutrients may benefit cardiometabolic health.

Specifically, n-3 fatty acid supplementation decreased CVD mortality (relative risk [RR]: 0.93; 95% CI: 0.88-0.97), myocardial infarction (RR: 0.85; 95% CI: 0.78-0.92), and coronary heart disease events (RR: 0.86; 95% CI: 0.80-0.93).
Folic acid supplementation decreased stroke risk (RR: 0.84; 95% CI: 0.72-0.97), and coenzyme Q10 supplementation decreased all-cause mortality events (RR: 0.68; 95% CI: 0.49-0.94).
Supplementation of some but not all micronutrients may benefit cardiometabolic health.

Systematic Reviewn=883,627

DOI

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 et al. • Clinical nutrition ESPEN (2025)

l-citrulline supplementation and watermelon intake overall lowered BP in middle-aged and elderly individuals.

The results indicate that l-citrulline supplementation and watermelon intake significantly reduced SBP (-4.02 mmHg [95 % CI: -6.54 to -1.50], P = 0.002) and DBP (-2.54 mmHg [95 % CI: -4.27 to -0.81], P = 0.004) in the elderly.
Subgroup analysis showed that the combined supplementation of l-citrulline and l-arginine significantly decreased SBP (-10.44 mmHg [95 % CI: -13.57 to -7.31], P < 0.00001) and DBP (-4.86 mmHg [95 % CI: -7.93 to -1.79], P = 0.002) in this population.
l-citrulline supplementation and watermelon intake overall lowered BP in middle-aged and elderly individuals.

Meta-Analysisn=415

DOI

Acute Effect of Citrulline Malate on Repetition Performance During Strength Training: A Systematic Review and Meta-Analysis

Vårvik FT et al. • International Journal of Sport Nutrition and Exercise Metabolism (2021)

Supplementing with 6-8g CitMal increased repetitions by 6.4% compared with placebo.

Small ergogenic effect (SMD=0.196)
3 ± 5 additional repetitions on average
Optimal dose 6-8g 40-60 min before exercise

Meta-Analysisn=198

DOI

Effects of Citrulline or Watermelon Supplementation on Body Composition: A Systematic Review and Dose-Response Meta-Analysis

Ashtary-Larky D et al. • Nutrients (2025)

CIT supplementation appears to have no overall effect on body composition.

Overall, CIT supplementation had no substantial effects on body mass index (BMI), body weight, fat mass (FM), waist circumference (WC), body fat percentage (BFP), and fat-free mass (FFM).
Interventions lasting 3 to 8 weeks were associated with a significant increase in FFM.
CIT supplementation appears to have no overall effect on body composition.

Meta-Analysis

DOI

Effect of citrulline on post-exercise rating of perceived exertion, muscle soreness, and blood lactate levels: A systematic review and meta-analysis

Rhim HC et al. • Journal of sport and health science (2020)

Citrulline supplements significantly reduced post-exercise RPE and muscle soreness without affecting blood lactate levels.

Citrulline supplementation significantly reduced RPE (n = 7, p = 0.03) and muscle soreness 24-h and 48-h after post-exercise (n = 7, p = 0.04; n = 6, p = 0.25, respectively).
However, citrulline supplementation did not significantly reduce muscle soreness 72-h post-exercise (n = 4, p = 0.62) or lower blood lactate levels (n = 8, p = 0.17).
Further research warranted to confirm findings

Meta-Analysisn=206

DOI

Effect of food sources of nitrate, polyphenols, L-arginine and L-citrulline on endurance exercise performance: a systematic review and meta-analysis of randomised controlled trials

d'Unienville NMA et al. • Journal of the International Society of Sports Nutrition (2021)

Foods rich in polyphenols and nitrate provide trivial benefits for endurance exercise performance, although these effects may be food dependent.

No effect on exercise performance following consumption of foods rich in L-citrulline was identified (SMD=-0.03, p=0.24).
Foods rich in polyphenols and nitrate provide trivial benefits for endurance exercise performance, although these effects may be food dependent.
Highly trained endurance athletes do not appear to benefit from consuming nitrate-rich foods but may benefit from polyphenol consumption.

Meta-Analysis

DOI

Effects of Citrulline Supplementation on Exercise Performance in Humans: A Review of the Current Literature

Gonzalez AM et al. • Journal of strength and conditioning research (2020)

Given the positive effects observed from some investigations, future studies should continue to investigate the effects of both acute and chronic supplementation with L-citrulline and citrulline malate on markers of blood flow and exercise performance and should seek to elucidate the mechanism underlying such effects.

Oral L-citrulline and citrulline malate supplementation have shown to increase plasma citrulline and arginine concentrations, along with total nitrate and nitrite concentrations.
Although blood flow enhancement is a proposed mechanism for the ergogenic potential of L-citrulline, evidence supporting acute improvements in vasodilation and skeletal muscle tissue perfusion after supplementation is scarce and inconsistent.
Nevertheless, several studies have reported that L-citrulline supplementation can enhance exercise performance and recovery.

Systematic Review

DOI

Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials

Mirenayat MS et al. • Current hypertension reports (2018)

The present systematic review and meta-analysis suggests that L-citrulline supplementation had no beneficial effect on blood pressure.

Meta-analysis examining L-Citrulline efficacy
Further research warranted to confirm findings

Meta-Analysis

DOI

[The effect of supplementation with L-arginine and L-citrulline on physical performance: a systematic review]

Huerta Ojeda Á et al. • Nutricion hospitalaria (2019)

However, there is not enough evidence to establish a beneficial L-citr dosage for physical performance.

All articles using a supplementation protocol with these amino acids, separately or in groups, were selected.
Results: a total of 38 articles were found, which were stratified according to the established protocol: a) supplementation with L-arg (n = 19); b) supplementation with L-arg and L-citr (n = 1); and c) supplementation with L-citr (n = 18), whether of short or prolonged duration.
Conclusion: there is evidence that L-citr works better as ergogenic than L-arg does on physical performance, since L-citr showed a positive effect on the rate of perceived exertion and muscular pain, in addition to a decrease in lactate concentrations and time in maximum tests.

Systematic Reviewn=19

DOI

Oral citrulline supplementation in pregnancies with preeclampsia: a multicenter, randomized, double-blind clinical trial

Winer N et al. • The American journal of clinical nutrition (2025)

The current trial found no benefit of oral L-citrulline supplementation to females with PE regarding either the duration of pregnancy, fetal growth, or maternal and neonatal outcomes.

The duration of pregnancy between inclusion and delivery was unaltered (hazard ratio: 0.90; 95% confidence interval: 0.62, 1.31).
Liver enzymes were higher on the day of delivery in the treated, compared to the placebo group (65.1 compared with 33.2 UI and 70.4 compared with 33.7 UI for alanine aminotransferase and aspartate aminotransferase, respectively, (estimate: 5.92; 95% confidence interval: 1.09, 10.74).
Systolic blood pressure (BP) was higher at delivery in the citrulline group compared with the control group (P = 0.015), whereas the diastolic BP showed no difference.

RCTn=115

DOI

Malate or Not? Acute Effects of L-Citrulline Versus Citrulline Malate on Neuromuscular Performance in Young, Trained Adults: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial

Martín-Olmedo JJ et al. • International journal of sport nutrition and exercise metabolism (2025)

This trial was registered at ClinicalTrials.gov (No. NCT05183893).

CIT and CMA supplementation did not enhance maximal neuromuscular performance (all p ≥ .061, ηp2≤.066), or ballistic strength (all p ≥ .348, ηp2≤.025).
In conclusion, CIT and CMA supplementation may not increase the neuromuscular performance during low- to moderate-volume resistance training sessions in young, trained adults.
This trial was registered at ClinicalTrials.gov (No. NCT05183893).

Crossovern=21

DOI

Changes in resistance training performance, rating of perceived exertion, and blood biomarkers after six weeks of supplementation with L-citrulline vs. L-citrulline DL-malate in resistance-trained men: a double-blind placebo-controlled trial

Bayat D et al. • Journal of the International Society of Sports Nutrition (2025)

Chronic citrulline supplementation seems to enhance upper body muscular endurance and post-exercise NOX response to RT, but there is no apparent difference between LC and CM in these aspects.

Chronic citrulline supplementation seems to enhance upper body muscular endurance and post-exercise NOX response to RT, but there is no apparent difference between LC and CM in these aspects.
Further research warranted to confirm findings

RCTn=33

DOI

Effects of Combined Versus Single Supplementation of Creatine, Beta-Alanine, and L-Citrulline During Short Sprint Interval Training on Basketball Players' Performance: A Double-Blind Randomized Placebo-Controlled Trial

Li M et al. • International journal of sports physiology and performance (2025)

Our findings indicate that short-term supplementation with Cr, BA, and L-Cit, as well as a combination of them during SSIT, can significantly improve the physical and physiological performance of basketball players compared to a PL.

All training groups (Cr, BA, L-Cit, combined, and PL) showed significant improvements in physical and physiological performance over the 4-week intervention (P < .05).
Further research warranted to confirm findings

RCTn=8

DOI

The Antioxidant Power of Bergamot Polyphenolic Fraction Gold Potentiates the Effects of L-Citrulline in Athlete Performance and Vasodilation in a Pilot Study

Mollace R et al. • Nutrients (2025)

Given the small sample size, this study serves as a pilot, and further research is needed to validate these findings on a larger scale.

No harmful adverse effects were observed.
Max supplementation, providing beneficial effects on the antioxidant state and preserving the vascular endothelium might be a supplementation strategy to improve athletic performance and potentiate results.
Given the small sample size, this study serves as a pilot, and further research is needed to validate these findings on a larger scale.

RCT

DOI

The impact of L-citrulline supplementation on glucose homeostasis, lipid profile, and some inflammatory factors in overweight and obese patients with type 2 diabetes: A double-blind randomized placebo-controlled trial

Azizi S et al. • Phytotherapy research : PTR (2021)

In conclusion, L-citrulline supplementation might improve glucose homeostasis, some lipid factors and inflammatory markers in overweight and obese patients with T2D.

L-citrulline supplementation decreased serum levels of insulin (p = .025), glucose (p = .032), HbA1c (p = .001), HOMA-IR (p = .037), TNF-α (p = .036), and hs-CRP (p = .027) significantly.
Moreover, no significant inter- and intra-group changes were observed for dietary intakes, anthropometric indices, total and low-density lipoprotein cholesterol levels (p > .05).
In conclusion, L-citrulline supplementation might improve glucose homeostasis, some lipid factors and inflammatory markers in overweight and obese patients with T2D.

RCTn=54

DOI

Effects of branched chain amino acids, l-citrulline, and alpha-glycerylphosphorylcholine supplementation on exercise performance in trained cyclists: a randomized crossover trial

Harrington RN • Journal of the International Society of Sports Nutrition (2023)

The combination of BCAAs, L-citrulline, and A-GPC used in this study improves cycling performance and may be useful for individuals seeking to improve athletic performance, particularly in disciplines requiring lower body muscular strength and endurance.

With the test supplement, there was an average increase in TT peak power of 11% and an average increase in time to fatigue of 36.2% in the HIEC test compared to the placebo.
There was no significant improvement in time to completion, average power, OMNI rating of perceived exertion, or VAS responses on perceived exertion in the TT test and no significant improvement in VAS measures of perceived exertion in the HIEC test.
The combination of BCAAs, L-citrulline, and A-GPC used in this study improves cycling performance and may be useful for individuals seeking to improve athletic performance, particularly in disciplines requiring lower body muscular strength and endurance.

Crossovern=30

DOI

CHronic hypERtension and L-citRulline studY (CHERRY): an Early-Phase Randomised Controlled Trial in Pregnancy

Ormesher L et al. • Reproductive sciences (Thousand Oaks, Calif.) (2024)

This rct examined the effects of L-Citrulline.

L-citrulline had no effect on diastolic BP (L-citrulline: - 1.82 95% CI (- 5.86, 2.22) vs placebo: - 5.00 95% CI (- 12.76, 2.76)), uterine artery Doppler or angiogenic biomarkers.
Although there was no effect on BP, retrospectively, this study was underpowered to detect BP changes < 9 mmHg, limiting the conclusions about biological effects.
Further research warranted to confirm findings

RCT

DOI

The effects of L-Citrulline and Glutathione on Endurance performance in young adult trained males

Cabre HE et al. • Journal of the International Society of Sports Nutrition (2023)

Acute ingestion of SPB after eight days may enhance blood flow, L-citrulline, and L-arginine plasma concentrations after high-intensity exercise, which may enhance performance.

Acute ingestion of SPB after eight days may enhance blood flow, L-citrulline, and L-arginine plasma concentrations after high-intensity exercise, which may enhance performance.
Further research warranted to confirm findings

RCTn=25

DOI

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