Evidence Level
Nitric Oxide
The nitric oxide (NO) pathway is a fundamental aspect of vascular physiology, as recognized by the 1998 Nobel Prize for its discovery. L-citrulline has been identified as an effective oral NO precursor due to its superior ability to elevate plasma arginine levels compared to arginine itself, as shown in studies by Schwedhelm et al. (2008). This is attributed to the extensive first-pass hepatic metabolism of arginine. A meta-analysis by Trexler et al. (2019) confirmed that citrulline supplementation enhances exercise performance across various modalities.
In the context of dietary nitrate, Siervo et al. (2013) demonstrated that beetroot-derived nitrate significantly lowers blood pressure through its conversion to nitrite and subsequently to NO via oral bacteria. Recent research has expanded the understanding of NO's role in health and disease. For instance, Campara et al. (2025) found elevated nitric oxide levels in endometriosis patients, particularly those with severe disease, suggesting a potential biomarker for disease severity.
Inhaled nitric oxide has shown promise in specific clinical settings. Zhou et al. (2025) reported that inhaled NO reduces mortality or bronchopulmonary dysplasia in premature infants, while Yan et al. (2024) found it decreases mechanical ventilation duration post-cardiac surgery. However, Kuitunen and Renko (2024) noted no significant reduction in hospital stay for acute bronchiolitis with inhaled NO, though they observed higher treatment-related harms.
These findings highlight the multifaceted role of nitric oxide in cardiovascular health, exercise performance, and clinical therapeutics, supported by robust evidence from systematic reviews and meta-analyses.