Benefits
Exercise performance
In a pooled analysis of 12 placebo-controlled studies in 198 healthy people, citrulline taken at least 30 minutes before high-intensity strength or sprint work gave a small benefit, although the result of every individual study overlapped with no effect. A pooled analysis of 9 endurance studies found no difference from control in time to exhaustion or time to finish.
Muscle soreness and perceived effort after exercise
Pooled data from 13 placebo-controlled trials in 206 healthy people, most often using 8 g of citrulline malate within 2 hours before exercise, found lower ratings of perceived effort and less muscle soreness 24 hours after exercise. Soreness was not lower at 48 or 72 hours, and blood lactate did not change.
Blood vessel function and blood pressure
Across 12 longer-term randomized trials, citrulline improved flow-mediated dilation, a measure of how well an artery widens, by 0.9 percentage points. A pooled analysis of 5 trials found no change in resting blood pressure, but a pooled analysis of 8 trials found systolic pressure 4.1 mmHg lower, with no clear change in diastolic pressure. In 16 overweight young men, 6 g a day for 14 days blunted rises in blood pressure and arterial stiffness during handgrip exercise and cold exposure, with no change at rest.
Erection hardness
In a single-blind study, 24 men with mild erection problems took a placebo for 1 month and then 1.5 g a day of L-citrulline for 1 month. Erection hardness rose from 3 to 4, the score the authors class as normal, in 12 men (50%) on citrulline versus 2 (8.3%) on placebo, and monthly intercourse rose. It is a single small study, the order of treatments was fixed rather than randomized, and no adverse events were reported.
Immune function in intensive care patients
In a randomized double-blind trial in 120 adults on breathing machines in intensive care, without sepsis, 5 g of citrulline every 12 hours by feeding tube for 5 days raised blood arginine but did not change organ function scores on day 7 or the immune markers measured. One author reported holding shares in a citrulline company.
Muscle mass and body composition
Pooled data from 21 randomized trials found no overall change in body weight, fat mass or fat-free mass with citrulline. Subgroups taking more than 6 g a day or aged over 40 showed less fat mass, and trials lasting 3 to 8 weeks showed more fat-free mass, but the authors describe these subgroup findings as exploratory.
Mechanism of action
Nitric Oxide (NO) Production
Oral L-arginine is partly broken down in the gut before it reaches the blood, while L-citrulline is readily absorbed and then converted to L-arginine; a dose-ranging study attributed this conversion to the kidneys. Arginine is the substrate nitric oxide synthase uses to make nitric oxide, which relaxes blood vessels. In healthy volunteers, citrulline raised blood arginine and urine markers of nitric oxide signaling (nitrate and cGMP), but did not improve flow-mediated dilation on its own.
Urea cycle and ammonia
Citrulline is an intermediate of the urea cycle, the route the body uses to dispose of ammonia, and oral citrulline raised blood ornithine and arginine, its neighbors in that cycle, in a dose-ranging study. Researchers have proposed ammonia buffering as one way citrulline might aid exercise, but the trials cited here did not measure ammonia, and pooled endurance studies found no performance change.
Clinical trials
Double-blind, randomized, placebo-controlled 2-way crossover trial (registry UMIN000014278): 2.4 g/day L-citrulline or placebo for 7 days, then 2.4 g 1 hour before the time trial on day 8. Funded by Kyowa Hakko Bio Co., Ltd., which employed three of the four authors (Suzuki et al. 2016, J Int Soc Sports Nutr)
22 trained men.
Plasma arginine rose, and 4-km completion time was 1.5% shorter than with placebo (p < 0.05). Self-rated muscle fatigue and concentration right after exercise were better than with placebo.
Systematic review and meta-analysis of 12 placebo-controlled studies (13 independent samples) giving at least 3 g of citrulline at least 30 minutes before testing, without other ergogenic ingredients (Trexler et al. 2019, Sports Med)
198 healthy men and women.
Citrulline beat placebo by a small pooled standardized mean difference of 0.20 (95% CI 0.01 to 0.39, p = 0.036), with low heterogeneity; the confidence interval of every individual study crossed zero.
Systematic review and fixed-effects meta-analysis of 9 randomized controlled trials of single-dose or loading citrulline in adults who were at least recreationally active (Harnden et al. 2023, J Int Soc Sports Nutr)
158 young healthy adults.
No significant difference from control in endurance time to exhaustion (pooled SMD 0.03, 95% CI -0.27 to 0.33) or time to completion (pooled SMD -0.07).
Systematic review and meta-analysis of five human trial arms reporting brachial or aortic blood pressure (Mirenayat et al. 2018, Curr Hypertens Rep)
Adults in five citrulline trial arms.
No significant change in brachial systolic (0.28 mmHg) or diastolic (-1.56 mmHg) blood pressure, or in aortic systolic or diastolic pressure. Body weight status explained part of the differences between studies.
Meta-analysis of randomized controlled trials of L-citrulline supplements or watermelon in adults; 12 trials assessed longer-term L-citrulline effects (Smeets et al. 2022, Br J Nutr)
Adults in 17 L-citrulline trials and 10 watermelon trials.
Longer-term L-citrulline improved brachial artery flow-mediated dilation by 0.9 percentage points (95% CI 0.7 to 1.1). No effects were found on vascular function after a single dose or on other cardiometabolic risk markers.
Single-blind study with a fixed sequence (not randomized): placebo for 1 month, then L-citrulline 1.5 g/day for 1 month (Cormio et al. 2011, Urology)
24 men with mild erectile dysfunction (erection hardness score 3), mean age 56.5.
Erection hardness score rose from 3 to 4 in 12 of 24 men (50%) on L-citrulline versus 2 of 24 (8.3%) on placebo (P < .01). Intercourse rose from 1.37 per month at baseline to 2.3 per month on L-citrulline (P < .01), with no change on placebo. No adverse events were reported.
Randomized, double-blind, multicenter trial (NCT02864017) of L-citrulline 5 g every 12 hours by nasogastric tube for 5 days versus an isonitrogenous, isocaloric placebo. Funded by the French Ministry of Health; the citrulline product came from Citrage, and one author reported being a Citrage Co. shareholder. (Tadié et al. 2023, Crit Care)
120 mechanically ventilated adults in four French intensive care units, without sepsis or septic shock.
Primary outcome null: organ dysfunction (SOFA) score on day 7 was 4 in both groups (p = 0.9). Plasma arginine rose on day 3, but immune markers (monocyte HLA-DR and interleukin-6) did not change.
Single-center, randomized, double-blind, placebo-controlled trial (NCT01995032) of 2500 mg L-citrulline plus 250 mg metformin, a prescription drug, three times a day for 26 weeks; citrulline was not tested alone. Funded by the Swiss National Science Foundation (Hafner et al. 2019, JAMA Netw Open)
47 ambulant boys aged 6.5 to 10 years with genetically confirmed Duchenne muscular dystrophy.
Primary outcome null: the transfer and standing posture motor score fell 4.0% on treatment versus 9.6% on placebo, a 5.5 percentage point difference that was not significant (P = .09). A prespecified subgroup of 29 boys who could walk 350 m in 6 minutes showed a smaller decline (P = .03). Timed function tests did not differ. Adverse effects were mild.