by Shawn J. Green, PhD
Blood-Pressure-Lowering Nitrate-Rich Veggie-Based Formulas May Slow COVID-19
Nitric oxide is naturally produced by the body and is best known for blood pressure homeostasis. In 1998, the Nobel Prize in Medicine was awarded to three scientists for discovering nitric oxide’s role as a key signaling molecule in the cardiovascular system.
Nitric Oxide Is Vital in Our Immune System
Nitric oxide is equally vital in our immune system. Viruses, mycobacteria, protozoans, bacteria, and fungi are among a growing list of microbes that are susceptible to nitric oxide (1–3). As a matter of fact, a series of in vitro studies have reported that nitric oxide inhibits SARS-CoV replication and interferes with viral infection (4–7).
Within the body, the magnitude and duration of nitric oxide synthesis determines whether the molecule’s actions are regulatory or cytotoxic. Low pulses of nitric oxide, produced by the endothelial cells lining our blood vessels, are involved with housekeeping events such as blood vessel tone, whereas large amounts of nitric oxide produced by certain types of immune cells, such as the macrophage, are often associated with a disease state. Under these circumstances, nitric oxide is either cytotoxic or protective (1).
As We Age, We Lose the Ability to Make Nitric Oxide
Unfortunately, as we grow older, we lose the ability to make nitric oxide which leads to cardio-metabolic problems and a possibly weakened immune system. If so, age-related nitric oxide deficiencies may partially explain why those individuals with comorbidities appear to be more susceptible to COVID-19.
However, the body has a ‘backup-system’ to produce nitric oxide through the chemical transformation of plant-derived inorganic nitrate. Elevated levels of nitric oxide after the consumption of nitrate-rich leafy green vegetables may explain why the DASH Diet is so effective at lowering blood pressure.
In essence, dietary inorganic nitrates, especially those derived from arugula, beets, among other leafy green vegetables, behave as a pro-drug in which the body converts inorganic nitrate to nitric oxide through a series of well-defined steps beginning with the friendly microflora on the tongue reducing nitrate to nitrite, which is subsequently reduced to nitric oxide in the gut, blood stream, and various organs throughout the body.
Enhancing the Body’s Nitric Oxide Production
A growing number of clinical studies have shown dietary inorganic nitrate from plant-based foods can be optimized to enhance nitric oxide production in the body and restore endothelial function. Such dietary sources and formulations are found to be safe in humans and effective at reducing elevated blood pressure in hypertensives. Interestingly, exhaled nitric oxide levels rose >200% in COPD patients who consumed nitrate-rich organic beet juice, hence the consumption of dietary inorganic nitrate results in elevated levels of nitric oxide within the lungs.
With that said, Mallinckrodt has partnered with the FDA, NIH, and the BARD to evaluate the anti-viral effects of inhaled nitric oxide gas (9). However, nitric oxide delivered directly to the lung as a gas should be closely monitored in a clinical setting due to the potentially harmful effects caused by the by-product, nitrogen dioxide, which may exacerbate lung inflammation of infected patients. Hopefully, the latter will not be the case and, instead, inhaled nitric oxide proves to be lifesaving.
A viable, safe, and effective alternative may actually be found with a nitric oxide-rich, plant-based formulary designed to inhibit COVID-19 replication and viral-cell fusion.
As we explore the merits of nitric oxide gas and the re-purposing of arthritis drugs by big pharma to diminish the symptoms of COVID-19, we should take a hard look at whether orally active nitrate formularies and plant-derived inorganic nitrate concentrates can slow down coronavirus infectivity if not reduce COVID-19 viral burden among infected individuals.
- Nitric oxide in mucosal immunity. S J Green. Nature Medicine1995, 1: 515–7.
- Does Nitric Oxide Play a Critical Role in Viral Infections? C Shoshkes Reiss, T Komatsu. Journal of Virology 1998, 72: 4547–4551
- Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals. T Akaike, Y Noguchi, S Ijiri, K Setoguchi, M Suga, Y M Zheng, B Dietzschold, and H Maeda. PNAS1996, 93:2448–53.
- Nitric Oxide Inhibits the Replication Cycle of Severe Acute Respiratory Syndrome Coronavirus. S Åkerström, M Mousavi, Jazi, J Klingström, M Leijon, Å Lundkvist, A Mirazi Journal of Virology 2005, 79 (3) 1966–69.
- Nitric oxide is elicited and inhibits viral replication in pigs infected with porcine respiratory coronavirus but not porcine reproductive and respiratory syndrome virus. K Jung, A Gurnani, GJ Renukaradhya, LJ Saif. Vet Immunol Immunopathol. 2010, 136:335–9.
- Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected. S Akerström, V Gunalan, CT Keng, YJ Tan, A Mirazimi. Virology 2009, 395:1–9.
- Inhibition of SARS-coronavirus infection in vitro by S-nitroso-N-acetylpenicillamine, a nitric oxide donor compound. E Kyaerts, L Vijgen, L Chen, P Maes, G Hedenstierna, M Van Ranst. Int J Infect Dis. 2004, 8: 223–6.
- Influence of dietary nitrate supplementation on lung function and exercise gas exchange in COPD patients. M Behnia, CM Wheatley, A Avolio, BD Johnson. Nitric Oxide2018, 76:53–61.
- Mallinckrodt Evaluates the Potential Role for Inhaled Nitric Oxide to Treat COVID-19 Associated Lung Complications, Engages with Scientific, Governmental and Regulatory Agencies. March 12, 2020, PRNEWSWIRE
Shawn J. Green published some of the very first discoveries in the early ’90s on how the immune system makes nitric oxide to combat intracellular pathogens such as leishmania, tularemia, and malaria.