tuneTypical Dose
1.5 g/day (mild ED context). 3–6 g/day in many sports/nutrition studies. BP trials commonly 3–9 g/day
Amino Acid
L-Citrulline
L-2-Amino-5-ureidovaleric acid
Evidence TierCWADA NOT PROHIBITED
watchEffect Window
Most short trials are null-to-small. Effects are modest and often protocol-dependent.
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
L-citrulline is converted to arginine and supports nitric oxide production more efficiently than oral arginine. It is used for exercise performance, muscle pump, blood pressure, and erectile function goals.
Evidence supports modest vascular effects more clearly than dramatic performance claims. Studies show small blood pressure reductions and some improvement in mild erectile-function settings, while exercise results remain mixed and seem more favorable in selected resistance-training protocols than in endurance tests. A smaller secondary literature also suggests possible metabolic and inflammatory benefits in type 2 diabetes, but that remains an exploratory use case rather than a primary reason to choose citrulline.
L-citrulline increases arginine pathway substrate handling via renal and urea-cycle related metabolism, making NO support plausible. Clinical performance translation remains inconsistent.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Acute/short-term pooled endurance outcomes are not consistently improved in healthy adults.
Secondary Outcomes
- Small blood-pressure lowering signal in selected trial subsets. Small pilot signal for mild erectile-function improvement at 1.5 g/day.
Safety
Contraindications and Interactions
Contraindications
- Pregnancy
- Lactation
- Severe renal/hepatic instability
- Unstable cardiovascular or psychiatric disease
Side effects
- Stomach discomfort
- Heartburn
Interactions
- Antihypertensives
- Nitrates
- PDE-5 inhibitors
- Vasodilatory supplements
Avoid if
- Active malignancy
- Unstable cardiovascular disease
- Unverified high-risk medication stacks
Evidence
Study-level References
l-citrulline-SRC-001Systematic review and meta-analysis of RCTs.
Sourceopen_in_newHarnden CS et al. "Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis." J Int Soc Sports Nutr. 2023;20(1):2209056. doi: 10.1080/15502783.2023.2209056; PMID: 37155582.
Population: 9 studies, n=158, young healthy adults, endurance protocols.
Dose protocol: Acute supplementation and short-duration loading regimens in RCTs.
Key findings: No significant pooled benefit on TTE (SMD 0.03 [−0.27, 0.33]) or TTC (SMD -0.07 [−0.50, 0.15]).
Notes: Young adult focus, acute-design bias, and protocol variability limit extrapolation to broader athlete cohorts.
Paper content
No significant pooled benefit on TTE (SMD 0.03 [−0.27, 0.33]) or TTC (SMD -0.07 [−0.50, 0.15]).
l-citrulline-SRC-002Meta-analysis of adult RCTs.
Sourceopen_in_newBarkhidarian B et al. "Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis." Avicenna J Phytomed. 2019;9(1):10-20. PMID: 30788274.
Population: 8 trials, doses 3–9 g/day, adults 22–71, intervention durations 1–17 weeks.
Dose protocol: Oral L-citrulline versus placebo/control.
Key findings: Directionally favorable systolic reduction (MD -4.10 mmHg), diastolic reduction not significant overall (MD -2.08 mmHg, CI crossed 0), with stronger DBP signal at ≥6 g/day.
Notes: Small trials, mixed comorbidity profiles, and potential publication bias. Effect size modest.
Paper content
Directionally favorable systolic reduction (MD -4.10 mmHg), diastolic reduction not significant overall (MD -2.08 mmHg, CI crossed 0), with stronger DBP signal at ≥6 g/day.
l-citrulline-SRC-003Single-blind clinical trial.
Sourceopen_in_newCormio L et al. "Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction." Urology. 2011;77(1):119-22. DOI: 10.1016/j.urology.2010.08.028; PMID: 21195829.
Population: 24 men with mild erectile dysfunction.
Dose protocol: 1 month placebo phase followed by 1.5 g/day citrulline for 1 month.
Key findings: 12/24 participants improved erection hardness score to normal on citrulline vs 2/24 on placebo.
Notes: Small sample, single-center, single-population trial, mild baseline severity only.
Paper content
12/24 participants improved erection hardness score to normal on citrulline vs 2/24 on placebo.
l-citrulline-SRC-004Official regulatory guidance pages.
Sourceopen_in_newWorld Anti-Doping Agency Prohibited List (official), https://www.wada-ama.org/en/content/what-is-prohibited; USADA prohibited list page https://www.usada.org/substances/prohibited-list/.
Population: Competition and sports-compliance governance context.
Dose protocol: Not applicable.
Key findings: No explicit public prohibited-substance listing found for L-citrulline as a standalone class. Requires annual compliance verification and supplement quality checks.
Notes: Absence in public list is not a contamination or purity guarantee. Rules are policy-level and update periodically.
Paper content
No explicit public prohibited-substance listing found for L-citrulline as a standalone class; requires annual compliance verification and supplement quality checks.
l-citrulline-SRC-005Systematic review and dose-response meta-analysis of 21 RCTs.
Sourceopen_in_newAshtary-Larky D, et al. Effects of Citrulline or Watermelon Supplementation on Body Composition: A Systematic Review and Dose-Response Meta-Analysis. Nutrients. 2025;17(19):3126. doi:10.3390/nu17193126. PMID:41097202.
Population: Adults across 21 RCTs.
Dose protocol: Citrulline or watermelon supplementation at varying doses across 21 RCTs.
Key findings: No overall effect on body composition. Subgroup signals for fat mass reduction in adults over 40 years and at doses above 6 g/day.
Notes: Dose-response meta-analysis. Subgroup findings are hypothesis-generating, not confirmatory.
Paper content
This dose-response meta-analysis of 21 RCTs found that citrulline supplementation had no overall effect on body composition. However, subgroup analyses revealed fat mass reductions in participants older than 40 years and those receiving doses greater than 6 g/day. Fat-free mass increases were observed in interventions lasting 3 to 8 weeks. These subgroup signals are hypothesis-generating but do not support a broad body composition claim for citrulline. The study is useful for framing the limits of citrulline's effects outside of its primary NO-mediated vascular role.
l-citrulline-SRC-006Systematic review.
Sourceopen_in_newGonzalez AM, Trexler ET. Effects of Citrulline Supplementation on Exercise Performance in Humans: A Review of the Current Literature. J Strength Cond Res. 2020;34(5):1480-1495. doi:10.1519/JSC.0000000000003426. PMID:31977835.
Population: Humans across multiple exercise studies.
Dose protocol: L-citrulline and citrulline malate at varying doses and durations in exercise studies.
Key findings: Reliably increased plasma citrulline, arginine, and NO-pathway biomarkers. Mixed exercise performance results with strongest signals in resistance exercise at 6 to 8 g citrulline malate.
Notes: Narrative systematic review. Useful for contextualizing the inconsistent performance evidence.
Paper content
This systematic review examined L-citrulline and citrulline malate supplementation effects on exercise performance. Supplementation reliably increased plasma citrulline, arginine, and total nitrate/nitrite concentrations. However, evidence for acute improvements in blood flow remained limited. Some studies demonstrated enhanced exercise performance and recovery, particularly in resistance exercise contexts, while endurance findings were mixed. The review supports citrulline as a NO precursor supplement with inconsistent but directionally positive ergogenic signals, particularly for high-volume resistance training at doses of 6 to 8 g citrulline malate.
l-citrulline-SRC-007Randomized double-blind placebo-controlled trial
Sourceopen_in_newAbbaszadeh F, Azizi S, Mobasseri M, Ebrahimi-Mameghani M. The effects of citrulline supplementation on meta-inflammation and insulin sensitivity in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Diabetol Metab Syndr. 2021;13(1):52. doi:10.1186/s13098-021-00669-w. PMID:33952324.
Population: Adults with type 2 diabetes receiving care at specialty clinics.
Dose protocol: 3 g/day before breakfast for 8 weeks in adults with type 2 diabetes.
Key findings: Fasting glucose, HbA1c, IL-6, and TLR-4 improved versus placebo, suggesting a modest metabolic and anti-inflammatory signal.
Notes: Best used as a secondary modernization source. It should not displace citrulline's main vascular and exercise framing.
Paper content
This small RCT broadens the citrulline picture beyond blood pressure and exercise. In adults with type 2 diabetes, 3 g/day for 8 weeks improved fasting glucose, HbA1c, inflammatory markers, and insulin-sensitivity indices. It is useful as a secondary metabolic signal, but it is not enough to make citrulline a primary diabetes treatment claim.