What medications and supplements increase nitric oxide (NO) levels?

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Last updated: February 12, 2025View editorial policy

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From the Guidelines

Medications and supplements that increase nitric oxide (NO) levels include L-arginine and NO donor drugs.

Key Findings

  • L-arginine is the substrate for NO synthesis and has been shown to increase NO levels in various studies 1.
  • Oral supplementation of L-arginine has been found to increase plasma L-citrulline, indicating enhancement of NO production, and improve hemodynamics and exercise capacity in patients with pulmonary arterial hypertension (PAH) 1.
  • L-arginine improves endothelium-dependent vasodilation in patients with hypercholesterolemia and atherosclerosis, and has been found to improve pain-free and maximal walking distance in patients with intermittent claudication 1.
  • NO donor drugs also increase NO levels, and therapies that target the NO pathway, such as phosphodiesterase type 5 (PDE5) inhibitors, have revolutionized the treatment of pulmonary hypertension 1.

Important Considerations

  • The effect of L-arginine on NO levels can vary depending on the dose and method of administration, and further clinical studies are needed to fully understand its effects 1.
  • Other supplements, such as ginkgo biloba and carnitine, may also have beneficial effects on NO levels and vascular health, but more research is needed to confirm their efficacy 1.

From the Research

Medications and Supplements that Increase Nitric Oxide (NO) Levels

  • L-arginine and L-citrulline supplementation contribute to nitric oxide levels, as L-arginine is directly involved in NO synthesis and L-citrulline acts as an L-arginine precursor 2
  • Beetroot juice has been reported to significantly increase plasma nitrite levels, regarded as markers of NO, after intake 2, 3
  • Nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are a class of drugs that release NO and have been shown to have innovative properties for the treatment of vascular disorders and cancer 4
  • Nitro-derivatives of flurbiprofen have shown encouraging results in models of Alzheimer's disease 4
  • Dietary nitrate supplementation can increase nitric oxide bioavailability, reduce blood pressure, and improve muscle contractile function in humans 3

Relationship Between Physical Activity and Nitric Oxide

  • Physical activity has been shown to enhance NO production, and exercise should be recommended for increasing the level of NO for athletes and for patients with cardiovascular disorders for therapy 5

Biomarkers of Nitric Oxide Bioavailability

  • Plasma nitrite concentration is the most often-used biomarker of NO bioavailability, but other biomarkers such as S-nitrosothiols (RSNOs) in whole blood and skeletal muscle nitrate may be more relevant in certain contexts 3
  • RSNOs in blood and skeletal muscle nitrate have been correlated with lower diastolic blood pressure and enhanced muscle contractile function following dietary nitrate supplementation 3

Regulation of Nitric Oxide Production

  • The cofactor tetrahydrobiopterin plays an important role in nitric oxide production, and its relation with arginine availability is a key factor in NO regulation 6
  • Dietary factors such as arginine or its precursors and vitamin C may have a modulating role in nitric oxide production 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Dietary supplements for improving nitric-oxide synthesis.

Journal of preventive medicine and hygiene, 2022

Research

Nitric oxide and its role in exercise physiology.

The Journal of sports medicine and physical fitness, 2021

Research

Regulation of nitric oxide production in health and disease.

Current opinion in clinical nutrition and metabolic care, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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