How the Body Makes Nitric Oxide
The two pathways your body uses to make nitric oxide, and why production declines as you age.
Your body produces nitric oxide through two main pathways: the eNOS pathway, in which an enzyme in the lining of your blood vessels produces nitric oxide and the dietary nitrate pathway, which converts nitrate from vegetables into nitric oxide with help from bacteria in your mouth. Both pathways help maintain healthy nitric oxide levels, and can be influenced by factors such as diet, exercise, and overall lifestyle habits.1
Nitric oxide (NO) is one of the most important molecules produced in the human body. It regulates many important cell functions, including regulation of healthy blood flow and healthy blood pressure levels, communication between cells in the brain, and how the body defends itself against pathogens.
Since the Nobel Prize–winning discovery identifying nitric oxide as a signaling molecule in the cardiovascular system, we now know there are two primary pathways for producing nitric oxide.1
Below, we explain both pathways, what can interfere with each, and how to support them.
What is the eNOS pathway?
The endothelial nitric oxide synthase (eNOS) pathway is one of the body's two primary pathways for producing nitric oxide. In this pathway, eNOS is an enzyme found in our endothelial cells, the cells that line all blood vessels throughout the body.
This enzyme converts the amino acid L-arginine into nitric oxide through a complex, multi-step reaction. Its activity tends to decline with age2; one commonly cited estimate is that eNOS is roughly half as active by around age 40.
If you smoke, don't exercise regularly, or eat a poor diet, the activity of this enzyme decreases further. Loss of this enzyme function is recognized as the earliest event in the progression of age related ailments. Research suggests that taking L-arginine may not be effective once this enzyme is impaired.
One way to help fix the eNOS pathway is to get moderate physical exercise regularly and eat foods with a high antioxidant capacity, which help protect nitric oxide from being broken down.
The two pathways at a glance:
|
Pathway |
Source of nitric oxide |
Declines with age? |
How to support it |
|
eNOS pathway |
An enzyme (eNOS) in the blood vessel lining converts L-arginine into nitric oxide |
Yes — activity tends to fall with age |
Regular exercise; antioxidant-rich foods |
|
Dietary nitrate pathway |
Dietary nitrate from vegetables to nitrite (via mouth bacteria) to nitric oxide |
No — but depends on diet and oral bacteria |
Dietary nitrate–rich foods; healthy oral bacteria |
What is the dietary nitrate pathway?
This food-enabled pathway (the nitrate–nitrite–nitric oxide pathway) is supported by a diet rich in dietary nitrate from beets and green leafy vegetables such as kale and spinach.1,3
Inorganic nitrate from vegetables is converted into nitrite by oral bacteria and then into nitric oxide by specific proteins and enzymes in the body.4
This pathway does not decline with age but is dependent upon our diet and the presence or absence of very specific oral nitrate reducing bacteria.5 If you do not eat enough nitrate enriched foods, this pathway is not functional. Furthermore, if you do eat plenty of nitrate rich foods but lack the right oral bacteria due to poor oral hygiene or use of antiseptic mouthwash, this pathway is not functional and you can become deficient in nitric oxide.
One way to help fuel the nitrate-to-nitrite-to-nitric oxide pathway is to eat foods high in dietary nitrate such as leafy greens like kale and spinach, and red beets — provided you have the right oral bacteria.
However, the dietary nitrate content of vegetables varies widely depending on where they're grown and the farming practices, so you may not get enough dietary nitrate from food alone to effectively support this pathway.
Maintaining a healthy oral microbiome is just as important. Overuse of antiseptic mouthwash, for example, may reduce the bacteria responsible for converting nitrate into nitrite, making this pathway less efficient.6
How does Humann support both nitric oxide pathways?
Lifestyle habits such as regular exercise and a diet rich in nitrate-containing vegetables remain the foundation for supporting healthy nitric oxide production. But when those habits aren't enough, targeted supplementation can help. Humann developed its nitric oxide products in collaboration with researchers at the University of Texas Health Science Center, building on decades of research into nitric oxide's role in cardiovascular health.
Our bestselling, nitric oxide supporting products include:
Neo40® is our clinically studied and patented formula that supports nitric oxide levels through both the eNOS and nitrate-nitrite pathways. Neo40 helps support the eNOS enzyme so that endothelial (endogenous) production of nitric oxide can improve, which may improve your body's own ability to make nitric oxide. Neo40 also increases nitric oxide production by the reduction of nitrite to nitric oxide.
SuperBeets® Heart Powder is the world's first and only beet root powder with patented nitric oxide technology born out of research from The University of Texas.
The beet root powder in SuperBeets Heart Powder is from high-quality non-GMO beets sustainably sourced from renowned growing regions, blended with a unique ratio of dietary nitrates and nitrites that can more effectively support Nitric Oxide production than other standard beetroot powders.
Remember, only specific oral nitrate reducing bacteria can convert dietary nitrates to nitrites. So if you do not have this specific bacteria in your mouth, you will not convert the nitrates from beetroot powder into nitrite and nitric oxide.
What sets SuperBeets apart from other beet products is that it relies heavily on nitrites to generate nitric oxide and is thus able to support nitric oxide production even in those who do not have the specific mouth bacteria.
This is an important distinction from other beet products which contain no or very little nitrite.
And because SuperBeets relies heavily on nitrites to generate nitric oxide, it also allows the product to work faster than other beet products.
Clinically studied Humann SPORT beet root powder also uses the dietary nitrate–nitrite pathway to support nitric oxide production. The patented formula cannot be duplicated and is trusted by the top 1% of athletes in the world.
Developed in partnership with the University of Texas Health Science Center's Nitric Oxide Discovery Program, SPORT Pre-Workout Powder helps your body produce nitric oxide by converting the dietary nitrate from beet root into nitric oxide.
Like SuperBeets® Heart Powder, SPORT Pre-Workout Powder can benefit everyone because it relies predominantly on a unique ratio of dietary nitrates and nitrites to generate nitric oxide — an important distinction from other beet products, which contain no or very little nitrite.
This allows SPORT Pre-Workout Powder to work faster than other beet products.
Oxidative stress from free radicals can inhibit eNOS activity, reducing your body's ability to produce nitric oxide and compromising your healthy nitric oxide levels over time.
SuperBeets Heart Chews help support the eNOS pathway with antioxidant-rich French grape seed extract, which has been clinically researched to help support healthy blood pressure nearly two times more effectively than diet and exercise alone.1
Your cardiovascular routine starts here.
Frequently asked questions
Can I get enough nitric oxide from food alone?
Sometimes, but not always. Leafy greens and beets are rich in dietary nitrate, but nitrate levels vary on how foods are grown and processed. The dietary nitrate pathway also depends on the right nitrate-reducing bacteria in your mouth.
Why doesn't beetroot work for everyone?
The dietary nitrate pathway depends on oral bacteria that convert nitrate to nitrite. Poor oral hygiene or antiseptic mouthwash can reduce these bacteria and blunt the effect. Formulas that supply nitrite directly can help support nitric oxide even when those bacteria are lacking.4
Does nitric oxide production really decline with age?
Yes. The eNOS pathway tends to become less active as we age, which is one reason older adults may benefit from supporting both pathways through diet, exercise, and targeted supplements.2
Sources
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Lundberg JO, Weitzberg E, Gladwin MT. The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics. Nature Reviews Drug Discovery. 2008;7:156–167. doi:10.1038/nrd2466.
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Pourbagher-Shahri AM, Farkhondeh T, Talebi M, Kopustinskiene DM, Samarghandian S, Bernatoniene J. An Overview of NO Signaling Pathways in Aging. Molecules. 2021;26(15):4533. doi:10.3390/molecules26154533. PMID 34361685; PMC8348219.
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Kapil V, Khambata RS, Robertson A, Caulfield MJ, Ahluwalia A. Dietary nitrate provides sustained blood pressure lowering in hypertensive patients. Hypertension. 2015;65(2):320–327. PMID 25421976.
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Govoni M, Jansson EA, Weitzberg E, Lundberg JO. The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash. Nitric Oxide. 2008;19(4):333–337. PMID 18793740.
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Rocha BS. The Nitrate-Nitrite-Nitric Oxide Pathway on Healthy Ageing: A Review of Pre-clinical and Clinical Data on the Impact of Dietary Nitrate in the Elderly. Frontiers in Aging. 2021;2:778467. doi:10.3389/fragi.2021.778467. PMID 35821990; PMC9261383.
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Kapil V, et al. Physiological role for nitrate-reducing oral bacteria in blood pressure control. Free Radical Biology and Medicine. 2013;55:93–100.
†In a 16-week controlled study involving 119 healthy men and women, SuperBeets Chews' polyphenol compound, taken as part of a healthy lifestyle was clinically shown nearly 2-times as effective at promoting normal blood pressure already in the normal range as healthy lifestyle alone.