Dietary supplements for improving nitric-oxide synthesis

J Prev Med Hyg. 2022 Oct 17;63(2 Suppl 3):E239-E245. doi: 10.15167/2421-4248/jpmh2022.63.2S3.2766. eCollection 2022 Jun.


Nitric oxide (NO) is an essential component of the human body, involved in blood vessel dilation, stimulation of hormone release, signaling and regulation of neurotransmission. Nitric oxide is synthesized by nitric-oxide-synthase-dependent and -independent pathways. Nitric oxide supplementation improves cardiac health, enhances performance during exercise, reduces high blood pressure during pregnancy, reduces erectile dysfunction and improves healing processes and respiratory response. Nitric-oxide-associated benefits are mostly apparent in untrained or moderately trained individuals. L-arginine and L-citrulline supplementation contributes to nitric oxide levels because L-arginine is directly involved in NO synthesis, whereas L-citrulline acts as an L-arginine precursor that is further converted to NO by a reaction catalyzed by NO synthase. L-arginine supplements increase respiratory response and enhance performance during exercise, while L-citrulline with malate and other molecules increase working capacity. Various studies involving beetroot juice have reported a significant increase in plasma nitrite levels, regarded as markers of NO, after intake of beetroot juice. Although NO supplementation may have mild to moderate side-effects, using smaller or divided doses could avoid some of these side-effects. Since nitric oxide supplementation may worsen certain health conditions and may interfere with certain medicines, it should only be taken under medical supervision.

Keywords: Dietary supplements; L- citrulline supplementation; L-arginine supplementation; Nitric oxide supplementation; Nitric oxide synthesis.

Publication types

  • Review

MeSH terms

  • Arginine
  • Dietary Supplements
  • Exercise*
  • Humans
  • Nitric Oxide*


  • Nitric Oxide
  • Arginine