REVIEW article
Front. Nutr.
Sec. Nutrition and Metabolism
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1648219
Interplay Between Dietary Nitrate Metabolism and Proton Pump Inhibitors: Impact on Nitric Oxide Pathways and Health Outcomes
Provisionally accepted
- 1Clinical Nutrition, College of Applied Medical Sciences-Jeddah, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- 2King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
- 3Clinical Nutrition, Umm Al-Qura University College of Applied Sciences, Makkah, Saudi Arabia
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Proton-pump inhibitors (PPIs) are often-prescribed antacids that are useful in the treatment of gastrointestinal disorders. Nonetheless, a number of studies have raised concerns about their long-term use, linking them to a higher risk of cardiovascular disease and other possible adverse effects, including brain damage. Since nitric oxide (NO) plays a vital role in neurological and vascular health, it is important to look into how PPIs might change the NO pathway. Oral bacteria and the preservation of a healthy stomach environment are essential for the external pathway's synthesis of NO, which involves dietary nitrates (NO₃⁻) and nitrites (NO2⁻). PPIs have been demonstrated to decrease stomach acidity, which decreases NO bioavailability and prevents dietary NO₃⁻ from being converted to NO2⁻ and, subsequently, to NO. Endothelial dysfunction, which is typified by decreased vasodilation and elevated vascular resistance—two major factors in the development of hypertension—may result from this drop in NO levels. Moreover, reduced NO levels are associated with impaired brain function since NO is necessary for maintaining cerebral blood flow, neuronal transmission, and overall cognitive functioning. We propose that PPIs influence nitrate metabolism by several potential mechanisms including PPI-induced hypochlorhydria and a change in oral and gastric microbiomes leading to dysbiosis. There may also be other contributing pathways. Understanding how PPIs impact the NO₃⁻-NO2⁻-NO pathway is crucial for assessing their long-term effects on cardiovascular and brain health. By comprehending this connection, we may more effectively weigh the potential systemic risks of PPIs against their therapeutic advantages for gastrointestinal disorders. This may also guide safer prescription practices and patient management measures.
Keywords: Dietary nitrate, Nitric Oxide, Proton Pump Inhibitors, vascular and brain health, microbiota
Received: 17 Jun 2025; Accepted: 18 Aug 2025.
Copyright: © 2025 Basaqr and Babateen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Reem o Basaqr, Clinical Nutrition, College of Applied Medical Sciences-Jeddah, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.