by Dr. Leo Galland

Recent research looks at the potential benefits of the amino acid L-citrulline, known as citrulline, as a workout recovery supplement and to help boost immunity after exercise.
Researchers at a University in Spain have found that citrulline can help preserve immune function after strenuous exercise. This is important because strenuous exercise causes a decline in immune function which starts when the exercise ends. The drop in immune function is associated with weakened function of white blood cells called PMN’s, which are the body’s first line of defense against infection.
The research team in Spain studied the effect of the amino acid L-citrulline on white blood cell function in elite cyclists before and after a race. Six thousand milligrams of L-citrulline malate (a heaping teaspoon of powder) prevented the decline in PMN function caused by a 3-hour race, when compared to placebo.
In research done in France, citrulline was shown to prevent post-exercise fatigue and muscle soreness in untrained athletes, when taken after exercise. This study indicates the potential beneficial use of citrulline as a workout recovery supplement.
However, a study done at the Human Performance Laboratory at East Carolina University found that the use of citrulline before exercise may impair performance of untrained athletes.
References and Abstracts:
Free Radic Res. 2009 Sep;43(9):828-35. Epub 2009 Jul 6.Effects of L-citrulline oral supplementation on polymorphonuclear neutrophils oxidative burst and nitric oxide production after exercise.Sureda A, Cordova A, Ferrer MD, Tauler P, Perez G, Tur JA, Pons A.Laboratori de Ciencies de l’Activitat Fisica, Departament de Biologia Fonamental i Ciencies de la Salut, Universitat de les Illes Balears, Palma de Mallorca, Illes Balears, Spain.
Seventeen volunteer male professional cyclists were randomly assigned to control or supplemented (6 g L-citrulline-malate) groups and participated in a cycling stage. Blood samples were taken in basal conditions, after the race and 3 h post-race. Citrulline supplementation significantly increased plasma concentration of both arginine and citrulline after the stage only in the supplemented group. Polymorphonuclear neutrophils (PMNs) from controls responded to exercise with a progressive decrease in ROS production. Supplemented PMNs significantly increased ROS production after exercise compared to basal values and diminished to values lower than basal at recovery. PMN nitrite concentration was significantly higher after exercise and recovery only in the supplemented group. Markers of oxidative damage-CK, LDH, malondialdehyde-and DNA damage remained unchanged in both groups. In conclusion, oral L-citrulline administration previous to a cycling stage increases plasma arginine availability for NO synthesis and PMNs priming for oxidative burst without oxidative damage.
Arzneimittelforschung. 1991 Jun;41(6):660-3.Activity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man.Callis A, Magnan de Bornier B, Serrano JJ, Bellet H, Saumade R.Department of Medical Biophysics, Institut de Biologie, Montpellier, France.
An experimental evaluation of citrulline malate (Stimol, CAS 54940-97-5), an anti-fatigue compound, was undertaken in man and in the animal in order to study the pharmacological activity of the substance at hepatic and renal level. In man, the protocol involved a double-blind randomized, placebo-controlled cross-over technique. The study in the animal was blind and placebo-controlled with two randomized parallel groups. Results showed that citrulline malate stimulates hepatic ureogenesis and favorizes the renal reabsorption of bicarbonates. These metabolic actions had a protective effect against acidosis and ammonia poisoning and explain the anti-fatigue properties of citrulline malate in man.
Med Sci Sports Exerc. 2006 Apr;38(4):660-6. L-citrulline reduces time to exhaustion and insulin response to a graded exercise test.Hickner RC, Tanner CJ, Evans CA, Clark PD, Haddock A, Fortune C, Geddis H, Waugh W, McCammon M.Human Performance Laboratory, East Carolina University, Greenville, NC 27858, USA. icknerr@mail.ecu.edu
PURPOSE: Oral L-arginine supplementation has been shown to improve treadmill time to exhaustion and resting insulin sensitivity in individuals with peripheral vascular disease and type 2 diabetes, respectively. Furthermore, L-citrulline supplementation increases plasma L-arginine concentration to a level higher than that achieved by oral L-arginine supplementation. The purpose of this investigation was therefore to determine whether time to exhaustion during a graded treadmill test, as well as plasma insulin and glucose profiles, could be improved with oral L-citrulline supplementation in healthy individuals.
METHODS: Seventeen young (18-34 yr), healthy male and female volunteers performed incremental treadmill tests to exhaustion following either placebo or citrulline ingestion (3 g 3 h before test, or 9 g over 24 h prior to testing).
RESULTS: Steady-state submaximal respiratory exchange ratio and VO2max were not significantly different between placebo and citrulline trials. Treadmill time to exhaustion was lower following citrulline ingestion than during placebo trials (888.2 +/- 17.7 vs 895.4 +/- 17.9 s; P < 0.05; N = 17), which was accompanied by a higher rating of perceived exertion during exercise in the L-citrulline compared with the placebo condition. There was also an increase in plasma insulin in response to this high-intensity exercise in the placebo, but not in the L-citrulline, condition (P < 0.05).
CONCLUSIONS: It can be concluded that, contrary to the hypothesized improvement in treadmill time following L-citrulline ingestion, there is a reduction in treadmill time following L-citrulline ingestion over the 24 h prior to testing. The normal response of increased plasma insulin following high-intensity exercise is also not present in the L-citrulline condition, indicating that L-citrulline ingestion may reduce nitric oxide-mediated pancreatic insulin secretion or increased insulin clearance.






















