Improvement of ventricular function in systolic heart failure patients with oral L-citrulline supplementation

Cardiol J. 2012;19(6):612-7. doi: 10.5603/cj.2012.0113.


Background: The utility of L-arginine and L-citrulline in treatment of arterial hypertension by increasing vascular oxide nitric availability has been demonstrated. Photoplethysmography, a simple and low-cost optical technique, makes it possible to assess vascular function and to detect changes in blood flow, pulse and swelling of the microvascular tissular space. The aim of the study was to evaluate the effect of L-citrulline supplementation on functional class, ejection fraction and peripheral blood flow in patients with systolic heart failure.

Methods: Thirty-five stable outpatients attending the Heart Failure Clinic at the INCMNSZ underwent clinical evaluation, radioisotopic ventriculography and photoplethysmography before and at the end of 4 months. They were randomized into two groups: experimental group, with oral L-citrulline supplementation (3 g/day, n = 20) and control group, without supplementation (n = 15).

Results: In the experimental group the left ventricular ejection fraction (LVEF) increased 20.3% at rest and 12.7% with stress, as well as the right ventricular ejection fraction at rest of 15.10% and 14.88% with stress. In addition, functional class improved in 35%, and the maximum amplitude time/total time (MAT/TT) index decreased 23.1%. These changes were statistically significant compared with the control group.

Conclusions: Citrulline supplementation significantly improved the LVEF, the endothelial function (MAT/TT index) and functional class. Citrulline can be an important co-adjuvant in the treatment of stable and stable systolic heart failure patients.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Aged
  • Arginine / administration & dosage*
  • Case-Control Studies
  • Citrulline / administration & dosage*
  • Dietary Supplements*
  • Endothelium, Vascular / drug effects
  • Female
  • Follow-Up Studies
  • Heart Failure, Systolic / diagnostic imaging
  • Heart Failure, Systolic / drug therapy*
  • Heart Failure, Systolic / physiopathology
  • Hemodynamics / drug effects
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / blood
  • Outpatients
  • Photoplethysmography
  • Radionuclide Imaging
  • Stroke Volume / drug effects
  • Treatment Outcome
  • Ventricular Function, Left / drug effects*


  • Citrulline
  • Nitric Oxide
  • Arginine