L-citrulline reduces time to exhaustion and insulin response to a graded exercise test

Med Sci Sports Exerc. 2006 Apr;38(4):660-6. doi: 10.1249/01.mss.0000210197.02576.da.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anaerobic Threshold / drug effects*
  • Analysis of Variance
  • Blood Glucose / metabolism*
  • Citrulline / administration & dosage*
  • Exercise Test*
  • Female
  • Humans
  • Insulin / blood*
  • Male
  • Plasma Volume


  • Blood Glucose
  • Insulin
  • Citrulline