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L-Citrulline Research & Evidence

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This content is for informational purposes only and does not constitute medical advice. Statements about dietary supplements have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease. Individual results may vary — consult your healthcare provider before starting any supplement. Full disclaimer

Evidence Level

Strong

L-Citrulline is an amino acid that enhances nitric oxide production and improves exercise performance. Unlike arginine, which undergoes significant first-pass liver metabolism, L-citrulline bypasses this process, leading to higher plasma arginine levels per gram consumed (Schwedhelm et al., 2008). This characteristic makes it a more efficient precursor for arginine, particularly in contexts where rapid nitric oxide production is desired.

Several studies have demonstrated the benefits of L-Citrulline supplementation. A systematic review and meta-analysis by Trexler et al. (2019) found that acute citrulline supplementation significantly enhances high-intensity strength and power performance. Additionally, Luo et al. (2025) reported that L-citrulline supplementation reduces systolic (-4.02 mmHg, P=0.002) and diastolic (-2.54 mmHg, P=0.004) blood pressure in middle-aged and older adults, highlighting its potential cardiovascular benefits.

Citrulline malate (2:1) is a popular form used in pre-workout supplements due to its enhanced bioavailability and effectiveness. However, pure L-citrulline at lower doses has also been shown to be equally effective in improving exercise performance (Trexler et al., 2019). While some studies suggest that L-Citrulline may not significantly impact inflammatory biomarkers or oxidative stress responses to exercise (Porto et al., 2023), its role as a nitric oxide booster and performance enhancer remains well-supported by evidence.

Evidence by Condition

ConditionStudied DoseEvidence
Exercise performance6-8 g citrulline malate pre-workoutStrong
Blood flow/NO production3-6 g L-citrulline dailyStrong
Blood pressure support3-6 g dailyModerate

References

  1. Meta-analysisTrexler ET, Persky AM, Ryan ED, et al. (2019). Acute effects of citrulline supplementation on high-intensity strength and power performance: a systematic review and meta-analysis. Sports Medicine. DOI PubMed
  2. RCTSchwedhelm E, Maas R, Freese R, et al. (2008). Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. British Journal of Clinical Pharmacology. DOI PubMed
  3. Meta-analysisLuo P, Chen J, Liu K, Zhang J (2025). 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.. Clinical nutrition ESPEN. DOI PubMed
  4. Meta-analysisPorto AA, Gonzaga LA, Benjamim CJR, Valenti VE (2023). 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.. Nutrients. DOI PubMed
  5. Meta-analysisd'Unienville NMA, Blake HT, Coates AM, Hill AM, et al. (2021). 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.. Journal of the International Society of Sports Nutrition. DOI PubMed
  6. Mirenayat MS, Moradi S, Mohammadi H, Rouhani MH (2018). Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials.. Current hypertension reports. DOI PubMed
  7. Luo P, Li Z, Liu K, Gao W (2025). Effects of L-citrulline supplementation and watermelon intake on arterial stiffness and endothelial function in middle-aged and older adults: a systematic review and meta-analysis of randomized controlled trials.. Frontiers in nutrition. DOI PubMed
Show 4 more references
  1. Huerta Ojeda Á, Domínguez de Hanna A, Barahona-Fuentes G (2019). [The effect of supplementation with L-arginine and L-citrulline on physical performance: a systematic review].. Nutricion hospitalaria. DOI PubMed
  2. Rodríguez-Carrillo AA, Espinoza-Vargas MR, Vargas-Ortiz K, Ibarra-Reynoso LDR, et al. (2025). 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.. Nutrients. DOI PubMed
  3. Li M, Sheykhlouvand M (2025). 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.. International journal of sports physiology and performance. DOI PubMed
  4. Tain YL, Hsu CN (2024). Oral citrulline supplementation in pregnancies with preeclampsia: a multicenter, randomized, placebo-controlled trial.. EClinicalMedicine. DOI PubMed