Skip to main content
Supplement ScienceSupplementScience

Nitric Oxide Side Effects & Safety

Evidence:Strong
·

This content is for informational purposes only and does not constitute medical advice. Statements about dietary supplements have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease. Individual results may vary — consult your healthcare provider before starting any supplement. Full disclaimer

Safety Profile

Overall safety rating: Generally Safe

Potential Side Effects

  • Generally well-tolerated at standard doses
  • Mild GI discomfort at high doses (>10g L-citrulline)
  • Possible headache from rapid vasodilation
  • Lightheadedness if combined with blood pressure medications
  • L-arginine may trigger herpes simplex outbreaks in susceptible individuals

Drug & Supplement Interactions

  • Blood pressure medications — additive hypotensive effects; monitor BP closely
  • PDE5 inhibitors (sildenafil, tadalafil) — both increase NO/cGMP signaling; may cause excessive vasodilation
  • Anticoagulants — NO has mild antiplatelet effects; use caution with blood thinners
  • Avoid mouthwash containing chlorhexidine before beetroot supplementation — it kills oral bacteria needed for nitrate-to-nitrite conversion

Maximum Dose

Do not exceed: 10g L-citrulline daily (higher doses not well-studied)

Looking for a well-tested Nitric Oxide?
All our top picks are third-party verified for purity
Full Nitric Oxide Guide

References

  1. RCTSchwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F, Boger RH (2008). Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. British Journal of Clinical Pharmacology. DOI PubMed
  2. Meta-analysisTrexler ET, Persky AM, Ryan ED, Schwartz TA, Stoner L, Smith-Ryan AE (2019). Acute Effects of Citrulline Supplementation on High-Intensity Strength and Power Performance: A Systematic Review and Meta-Analysis. Sports Medicine. DOI PubMed
  3. Meta-analysisSiervo M, Lara J, Ogbonmwan I, Mathers JC (2013). Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis. Journal of Nutrition. DOI PubMed
  4. RCTCormio L, De Siati M, Lorusso F, Selvaggio O, Mirabella L, Sanguedolce F, Carrieri G (2011). Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. DOI PubMed
  5. Meta-analysisCampara K, Rodrigues P, Viero FT, da Silva B, et al. (2025). Nitric oxide as a biomarker for patients with endometriosis: a systematic review and meta-analysis.. Nitric oxide : biology and chemistry. DOI PubMed
  6. Zhou K, Xu W, Li D, Lao C, et al. (2025). Inhaled nitric oxide in preterm infants with respiratory disease: a systematic review and meta-analysis.. European journal of medical research. DOI PubMed
  7. Zinellu A, Tommasi S, Carru C, Sotgia S, et al. (2024). A systematic review and meta-analysis of nitric oxide-associated arginine metabolites in schizophrenia.. Translational psychiatry. DOI PubMed
Show 3 more references
  1. Kuitunen I, Renko M (2024). Inhaled nitric oxide in acute bronchiolitis: A systematic review and meta-analysis.. Pediatric pulmonology. DOI PubMed
  2. Dahlan AF, Islam MA, Shukri NM, Abdullah B (2024). Nasal nitric oxide measurement in allergic rhinitis and non-allergic rhinitis: a meta-analysis.. Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale. DOI PubMed
  3. Zheng Y, Wu Q, Han S (2023). Inhaled nitric oxide in premature infants for preventing bronchopulmonary dysplasia: a meta-analysis.. BMC pediatrics. DOI PubMed