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L-Citrulline Side Effects & Safety

Evidence:Strong
·

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

Safety Profile

Overall safety rating: Generally Safe

Potential Side Effects

  • Very well tolerated
  • Mild GI discomfort at high doses (>10 g)
  • Rare headache from vasodilation

Drug & Supplement Interactions

  • PDE5 inhibitors (Viagra, Cialis) — additive vasodilatory effects; may cause excessive blood pressure drop
  • Blood pressure medications — may enhance hypotensive effects
  • Nitrate medications — additive NO-mediated vasodilation

Maximum Dose

Do not exceed: 10 g/day L-citrulline has been used safely; GI discomfort may increase at higher doses

Full L-Citrulline Guide

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