Benefits
Resistance Training Performance
Citrulline malate 8 g pre-workout significantly increased reps to failure on bench press in a single crossover study (Perez-Guisado 2010, n=41). This figure is widely cited but not robustly replicated; a 2022 systematic review and meta-analysis (Aguiar & Casonatto) found no statistically significant overall effect on muscle strength.
Reduced Post-Exercise Soreness
A single crossover study (Perez-Guisado 2010) reported a 40% reduction in self-rated muscle soreness at 24-48 hours post-exercise vs placebo; this widely cited figure has not been robustly replicated. Mechanism: improved blood flow, ammonia clearance, ATP regeneration support via malate.
Endurance / Aerobic Performance Modest Effects
Some trials show modest endurance improvements; effect smaller than resistance training benefits, including improved cycling time-trial performance.
Increased Plasma Arginine and NO
Citrulline raises plasma arginine more effectively than oral arginine itself (citrulline bypasses first-pass intestinal arginase). Increased arginine supports nitric oxide synthesis. Foundational pharmacology for vasodilation and 'pump' effects.
Blood Flow / Sexual Function Support (Preliminary)
A small pilot study reported that L-citrulline 1.5 g/day supported erection hardness in men with mild difficulties, consistent with nitric-oxide pathway support. This is preliminary single-study evidence, not a treatment for any medical condition; men with erectile concerns should consult a clinician.
Mechanism of action
Citrulline-to-Arginine Conversion
Oral L-CITRULLINE is converted to L-ARGININE in the kidney via argininosuccinate synthase + lyase. Bypasses intestinal arginase that breaks down oral arginine — citrulline raises plasma arginine more effectively than oral arginine itself. Arginine is substrate for nitric oxide synthase.
Nitric Oxide / Vasodilation
Increased arginine → increased nitric oxide → vasodilation, increased blood flow, improved nutrient and oxygen delivery to muscles. Mechanism for 'pump' effects and endurance support.
Malate / Krebs Cycle Substrate
Malate (malic acid) is intermediate in Krebs cycle (citric acid cycle) — supports ATP regeneration. Theoretical contribution to fatigue resistance.
Ammonia Clearance (Urea Cycle)
Citrulline is intermediate in urea cycle; supplemental citrulline supports clearance of ammonia (a fatigue metabolite). May contribute to performance effects.
Clinical trials
Crossover clinical trial of citrulline malate (8 g, 60 min pre-workout) vs placebo for chest workout performance.
41 men.
Reported significantly more repetitions in the later (fatigued) sets and a 40% reduction in soreness at 24-48 hours. Single crossover study; these often-quoted figures are widely cited but not robustly replicated, and a 2022 meta-analysis found no significant overall strength effect.
Clinical trial of citrulline malate (12 g/day for 7 days) on cycling time trial performance.
12 men.
Modest improvement in 4-km time trial performance and reduced perceived exertion. Effect smaller than resistance training benefits.