NO’s far-reaching influence on health

NO was the first gas ever discovered to act as a signaling molecule—a molecule that communicates with cells, giving them directions on how to behave—in humans it is found throughout the body, from the endothelial lining of our blood vessels to the brain to immune cells.¹ It is a potent vasodilator (i.e., it relaxes the arteries) that reduces blood pressure and improves circulation, increasing blood flow and oxygen delivery to every part of the body. It also regulates mitochondrial function and stimulates mitochondrial biogenesis, or the creation of new mitochondria.² Mitochondria are necessary for energy production in our cells and play a huge role in overall health. As one Harvard researcher put it, “…just about every cellular process is linked to mitochondria.”³ 

NO has been found to positively influence cardiovascular health, exercise performance, cognitive function, and sexual performance. It is critical for proper immune function, it supports healthy insulin production and function, and is involved in bone health.^{4 5 6} It truly is a major player in whole-body health. 

Cardiovascular Health

In addition to improving vasodilation, NO also prevents platelet aggregation and adhesion (blood clots) and protects the arteries from age-related changes such as stiffness, endothelial dysfunction, oxidative stress, and inflammation.^{7 8} One study with hypertensive subjects found that just a little over a cup of beetroot juice—a concentrated source of dietary nitrate, which the body easily converts to NO—each day improved blood pressure and endothelial function, and reduced arterial stiffness over the course of four weeks.⁹ 

Erectile Dysfunction

Erectile dysfunction, or ED, is now recognized as an early indicator of cardiovascular disease, and indeed, men with ischemic heart disease have a high prevalence of ED.¹⁰ When the arteries that supply the penis with blood to achieve and maintain an erection are blocked or hardened, or the lining of these arteries are damaged, blood flow is reduced. Just as NO is essential for maintaining healthy vasodilation and blood flow, NO is also believed to be essential for a normal erection and impaired NO activity is directly related to ED.¹¹ 

Brain Function

In addition to keeping the blood vessels to the brain functioning optimally, NO helps to maintain nerve cells, regulate normal brain functions, and increase blood flow to the brain.^{12 13} In one study, older adults with an average age of 74 were put on a high-nitrate diet that included two cups of beetroot juice at breakfast and a spinach and beetroot salad at dinner. In just two days, those on the high-nitrate diet experienced an increase in blood flow to the frontal lobe, the part of the brain involved in memory, attention, and regulating emotions, and an area at risk for reduced blood supply in the elderly.¹⁴ Other recent research found that when hypertensive senior adults took a shot of beetroot juice (containing 560 mg of nitrate) just before walking, they experienced brain activity that closely resembled that of younger adults, specifically in the somatomotor cortex, the area responsible for processing information from the muscles.¹⁵ 

Exercise Performance

Across age ranges, in trained and untrained athletes, males and females, and a variety of different activities, dietary nitrate—typically in the form of beetroot juice—helps muscles work more efficiently and use less oxygen, and increases tolerance to exercise, all of which improve overall performance and increases the time to exhaustion.^{16 17} 

Digestive Health

NO plays many roles in the digestive tract where it increases the mucosal lining, which helps to protect the GI tract from pathogens, as well as keep intestinal cells healthy. It is also crucial to gut motility and may even protect against increased permeability (leaky gut) and oxidative damage.^{18 19 20} 

Diet

Most studies investigating the health effects of NO utilize beetroot juice or beetroot powder in water to maximize NO levels in the subjects. Nitrate-rich foods, like beets, provide a concentrated dose of dietary nitrate which the body can easily convert to NO. Additionally, research has shown that beetroot juice influences the balance of bacteria in the mouth in a positive way, shifting to more beneficial bacteria associated with vascular and cognitive health and decreasing bacteria associated with disease and inflammation.²¹ Be aware that NO has a short half-life (it’s reduced in the body pretty quickly), so it’s important to strive to maintain consistent levels. You can do this by regularly eating high-nitrate foods, such as beets, spinach, and arugula, and by utilizing specific supplements, like beetroot juice or powder, to consistently enhance NO levels (test strips are readily available and help gauge your levels). For all of the many health benefits this molecule offers, are you ready to say yes to NO?

In addition to beetroot juice or powder, other supplements that effectively increase NO levels include grapeseed extract,^{22 23} Pycnogenol,²⁴ L-citrulline,²⁵ chlorella,²⁶ and spirulina.²⁷

References

1. https://www.nobelprize.org/nobel_prizes/medicine/laureates/1998/press.h…
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3. https://www.livescience.com/47979-mighty-mitochondria-nigms.html
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9. Kapil V, Khambata RS, Roberston A, Caulfield MJ, Ahulwalia A. Dietary nitrate provides sustained blood pressure lowering in patients. Hypertension. 2015;65:320-327.  http://hyper.ahajournals.org/content/65/2/320.long
10. Sullivan M, Thompson C, Dashwood M, et al. “Nitric oxide and penile erection: Is erectile dysfunction another manifestation of vascular disease?” Cardiovascular Research. 1999 Aug;43(3): 658-665. https://academic.oup.com/cardiovascres/article/43/3/658/321047
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15. Petrie M, Rejeski W. Jack, Basu S, et al. “Beet Root Juice: An Ergogenic Aid for Exercise and the Aging Brain.” The Journals of Gerontology 2017 Sept; 72 (9): 1284-1289 https://academic.oup.com/biomedgerontology/article/72/9/1284/2452303
16. Affourtit C, Bailey SJ, Jones AM, et al. On the mechanism by which dietary nitrate improves human skeletal muscle function. Front Physiol. 2015;6:211. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518145/
17. Clements WT, Lee SR, Bloomer RJ. Nitrate ingestion: a review of the health and physical performance effects. Nutrients. 2014 Nov;6(11):5224-5264. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245587/
18. Paterson WG. Esophageal peristalsis. GI Motility Online. May 16 2006: 10.1038/gimo13. https://www.nature.com/gimo/contents/pt1/full/gimo13.html
19. Petersson J, Phillipson M, Jansson E, et al. Dietary nitrate increases gastric mucosal blood flow and mucosal defense. Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G718-24. https://www.ncbi.nlm.nih.gov/pubmed/17082222  
20. Magierowski M, Magierowska K, Kwiecien S, Brzozowski T. Gaseous mediators nitric oxide and hydrogen sulfide in the mechanism of gastrointestinal integrity, protection and ulcer healing.  Molecules. 2015 May;20(5):9099-9123. https://www.ncbi.nlm.nih.gov/pubmed/25996214
21. Vanhatalo, A., L’Heureux, J.E., Kelly, J., Blackwell, J.R., Wylie, L.J., Fulford, J. Winyard, P.G., Williams, D.W., van der Giezen, M. Jones, A.M. (2021). Network analysis of nitrate-sensitive oral microbiome reveals interactions with cognitive function and cardiovascular health across dietary interventions. Redox Biology, 41, 101933. doi: 10.1016/j.redox.2021.101933
22. Feng Z, Wei RB, et al. “Grape seed extract enhances eNOS expression and NO production through regulating calcium-mediated AKT phosphorylation in H202-treated endothelium.” Cell Biol Int. 2010 Oct, 34(10): 1055-61.
23. Clifton PM. “Effect of Grape Seed Extract and Quercetin on Cardiovascular and Endothelial Parameters in High-Risk Subjects.” J Biomed Biotechnol. 2004;2004(5): 272-278
24. Nishioka K, Hidaka T, Nakamura S, et al. “Pycnogenol, French maritime pine bark extract, augments endothelium-dependant vasodilation in humans.” Hypertens Res. 2007 Sep; 30(9): 775-80.
25. Ochiai M, Hayashi T, et al. “Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men.” Int J Cardiol. 2012 Mar 8;155(2): 257-61
26. Otsuki T, Shimizu K, Maeda S. “Changes in arterial stiffness and nitric oxide production with Chlorella-derived multicomponent supplementation in middle-aged and older individuals.” J Clin Biochem Nutr. 2015 Nov;57(3): 228-32
27. MA Juarez-Oropeza, D. Mascher, et al. “Effects of Dietary Spirulina on Vascular Reactivity.” Journal of Medicinal Food. March 2009, 12(1): 15-20.