Synergetic Effect of NO Precursor Supplementation and Exercise Training

Med Sci Sports Exerc. 2020 Nov;52(11):2437-2447. doi: 10.1249/MSS.0000000000002387.


Introduction: Nitric oxide (NO) precursor supplementation has been shown to increase NO bioavailability and can potentially improve vascular function and exercise performance. It remains unclear whether the combination of NO precursor supplementation and exercise training has synergic effects on exercise performance. This study aims to assess the effect of chronic nitrate and citrulline intake on exercise training adaptations in healthy young individuals.

Methods: In this randomized, double-bind trial, 24 healthy young (12 females) subjects performed vascular function assessment (blood pressure, pulse wave velocity, postischemia vasodilation, and cerebrovascular reactivity) and both local (submaximal isometric unilateral knee extension) and whole-body (incremental cycling) exercise tests to exhaustion before and after a 2-month exercise training program and daily intake of a placebo or a nitrate-rich salad and citrulline (N + C, 520 mg nitrate and 6 g citrulline) drink. Prefrontal cortex and quadriceps oxygenation was monitored continuously during exercise by near-infrared spectroscopy.

Results: N + C supplementation had no effect on vascular function and muscle and cerebral oxygenation during both local and whole-body exercise. N + C supplementation induced a significantly larger increase in maximal knee extensor strength (+5.1 ± 3.5 vs +0.2 ± 5.5 kg, P = 0.008) as well as a trend toward a larger increase in knee extensor endurance (+35.2 ± 26.1 vs +24.0 ± 10.4 contractions, P = 0.092) than placebo, but no effect on exercise training-induced maximal aerobic performance improvement.

Conclusion: These results suggest that chronic nitrate and citrulline supplementation enhances the effect of exercise training on quadriceps muscle function in healthy active young individuals, but this does not translate into improved maximal aerobic performances.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Adult
  • Citrulline / administration & dosage*
  • Dietary Supplements*
  • Double-Blind Method
  • Exercise / physiology*
  • Exercise Test
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Muscle Strength / drug effects*
  • Nitrates / administration & dosage*
  • Nitric Oxide / metabolism*
  • Physical Endurance / drug effects*
  • Vasodilation / drug effects
  • Young Adult


  • Nitrates
  • Citrulline
  • Nitric Oxide