Nitric oxide supplement research is more promising than many people expect—but the gap between clinical evidence and what supplement companies actually deliver is striking. This article breaks down the research on the main nitric oxide-boosting strategies, covers what the clinical trials actually show, and examines one cautionary case study in detail so readers can evaluate nitric oxide products with clear, evidence-based criteria. The bottom line: the science on dietary nitrate is genuinely interesting, but most supplements fail to deliver the doses used in clinical trials—and some actively mislead consumers about the evidence supporting them.
Table of Contents
The Background Story
Why did scientists become interested in nitric oxide supplements in the first place? And are there any proven benefits? It all started with an unexpected discovery.
Workers with angina in Alfred Nobel's dynamite factories in the late 1860s noticed something mysterious. Their angina improved during the work week, but returned on weekends. The culprit was nitroglycerin. Physicians realized it caused blood vessels to relax, opening them wider and relieving pressure [1].
The mechanism wasn't discovered until the 1970s: nitric oxide, produced as nitroglycerin breaks down, relaxes the smooth muscle cells lining blood vessel walls [1].
By the 1980s, scientists had established that nitric oxide is a crucial signalling molecule in the cardiovascular system. Three researchers earned a Nobel Prize for the discovery in 1998 [1].
Because of its ability to relax blood vessels, nitric oxide plays a key role in the control of blood flow and blood pressure. It also supports heart muscle function, helps regulate blood clotting, and has other important functions [2].
This emerging understanding of nitric oxide sparked interest among supplement makers. Increasing blood flow could enhance oxygen and nutrient delivery, leading to better exercise performance and a greater impact from training.
There is another factor adding urgency to this area. The body's ability to produce nitric oxide declines with age [3].
Disruption of nitric oxide production has been linked to an array of age-related problems in areas as diverse as heart, brain, reproductive, and muscle health [4]. This makes the question of how to maintain adequate nitric oxide production over time a clinically relevant one—not just an athletic performance concern.
Even if there is a clear potential benefit to increasing nitric oxide levels, there is a fundamental challenge to overcome. Nitric oxide cannot simply be swallowed. It is an extremely unstable gas—in the body, it reacts immediately with other substances and is gone almost instantly [5]. This is by design: the very instability that makes it such a precise signalling molecule also makes it impossible to deliver directly in a supplement capsule.
This delivery problem was solved by pharmaceutical manufacturers some time ago. Clinical medications like GTN (glyceryl trinitrate) sprays and ISMN (isosorbide mononitrate) result in the production of nitric oxide where it is needed in blood vessel walls. But these are prescription medications with known side effect profiles, not something available over the counter.
Moreover, there is an Achilles' heel with medications like ISMN. The body rapidly builds tolerance when patients take them, and they lose much of their effectiveness over time [6]. Patients often have to take medication-free intervals to restore their sensitivity.
That is because of how these drugs work. They do not support the body's own nitric oxide system—they bypass it. They act more like short-acting jolts that force blood vessels to relax. Over time, the body adapts and stops responding.
Supplement developers took a different approach. Instead of forcing nitric oxide from outside, they asked: what if the body's built-in nitric oxide pathway could be supported directly?
That way, a supplement could be taken long-term without losing its effect, potentially helping to counter the natural decline in nitric oxide production that comes with age. It would act as a tool that may help support one of the systems linked to healthy aging—not a pharmaceutical substitute.
Supplements
The logic makes sense. But how has it worked out in practice? Here is a look at the main strategies supplement manufacturers have used to enhance nitric oxide production, and what the research actually shows.
The most common ingredient in nitric oxide supplements—often called "nitric oxide boosters"—is L-arginine. It is an amino acid that is a key ingredient in the primary pathway for nitric oxide production in the body [7].
Many human studies have examined L-arginine supplements:
- No effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletes [8]
- Bolus Arginine Supplementation Affects neither Muscle Blood Flow nor Muscle Protein Synthesis in Young Men at Rest or After Resistance Exercise [9]
- Acute L-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise tolerance [10]
While L-arginine blood levels rise with supplementation, this has not reliably translated into athletic performance improvements or meaningfully raised nitric oxide levels in the blood. The body tightly regulates arginine metabolism, and simply flooding the system with more arginine does not appear to push more through the nitric oxide synthesis pathway in healthy individuals.
That is where L-citrulline comes in. L-citrulline is converted to L-arginine in the kidneys after ingestion, and research has shown it is actually more effective than L-arginine itself at raising blood arginine levels [11]. Because it bypasses the gut and liver metabolism that degrades a large fraction of oral L-arginine, citrulline delivers more arginine to circulation per gram consumed. Could this more efficient delivery succeed where L-arginine failed?
Unfortunately, the research has been underwhelming here too when it comes to exercise performance. For example, a study tested L-citrulline in healthy young adults to see if it would increase time to exhaustion during exercise. It did not [12]. The arginine-to-NO translation problem appears to persist even when blood arginine levels are raised more effectively.
However, a 2019 meta-analysis did find that L-citrulline appears to slightly reduce blood pressure when the dose was at least 6 g/day—though the effect size is modest, and it is not a clinically dramatic result [13].
More recently, the research focus has shifted to nitrate supplements, which target a newly discovered pathway for supplying nitric oxide to cells.
Dietary nitrate (with an 'a'), found naturally in leafy greens, is converted into nitrite (with an 'i') by bacteria on the tongue, and further modified through digestion to eventually produce nitric oxide in the blood [14].
A popular type of supplement in this category is derived from beets, since they are naturally rich in nitrate [15].
Do supplements targeting this pathway actually work? In clinical trials, results have been encouraging. An important 2014 study tested the effects of a daily dose of beetroot juice containing approximately 397 mg of nitrate against a placebo in patients with high blood pressure [16].
The study found that beetroot juice supplementation significantly reduced blood pressure by around 8 points—an effect size comparable to blood pressure medication, representing a meaningful reduction in stroke and heart attack risk [16].
The study also found that the beetroot juice supplement improved blood vessel function and stiffness [16].
Another study found that just one week of daily doses of beetroot juice containing 378 mg of nitrate significantly improved exercise endurance and blood pressure metrics in elderly patients with heart failure [17].
Cautionary Tale: Nitralis
Here is where caution is warranted. Just because a substance shows benefit in a clinical trial does not mean supplement companies will use it properly in their products. The following case study illustrates how misleading the gap can be—and what to look for when selecting a nitrate supplement.
The product is called Nitralis from DoNotAge. It is based on the nitrate pathway discussed above, with fermented beet as the primary ingredient [19].
On their website, DoNotAge lists four claims for Nitralis. It supposedly:
- Is clinically proven to boost nitric oxide levels and vascular performance
- Boosts circulation and vascular health
- Enhances physical performance
- Supports cognitive function [19]
The research discussed above does show that boosting nitric oxide levels can be linked to some of these benefits—particularly blood flow, vascular health, and endurance during exercise.
But what about cognitive function? The basic theory is that increasing blood flow to the brain should help with certain aspects of cognitive performance. It makes sense in theory. But actual data from randomized clinical trials is mixed. Though there have been some positive results, a meta-analysis concluded that, overall, the evidence does not show that nitrate supplements impact cognitive function or blood flow in the brain [18].
There is therefore a significant question mark over the cognitive function claim in particular. Supplement companies frequently stretch the evidence—but with Nitralis, the problems extend well beyond optimistic marketing language.
Returning to the impacts on blood flow, vascular health, and endurance: the clinical trial evidence, as reviewed above, does support nitrate-based beet supplements at adequate doses. But what about this specific product and its specific trial?
Notice a key claim for Nitralis: it is "clinically proven to boost nitric oxide levels and vascular performance." That implies there is a clinical trial. Here is what that trial actually contains [19].
The clinical trial in question was published in the Biomedical Journal of Scientific & Technical Research [19].
Before examining the study itself, several red flags are worth noting. First, the article was received on October 3 and published just two weeks later—an extraordinarily fast turnaround for a scientific journal. The peer-review process typically takes months, suggesting a publication more interested in volume than quality. The journal itself does not have an impact factor.
The institutional affiliation listed is also telling: DoNotAge.org is described as a "Health Research Organization." In reality, it is a supplements company.
When supplement or pharmaceutical companies sponsor clinical trials, there should be a clear separation between the trial sponsor and whoever actually conducts the research and collects the data. Independent researchers running the trial protect against the sponsor influencing results.
As a point of comparison, consider a properly designed trial: the researcher writes the trial protocol, applies for and receives independent ethics approval, crowdfunds the study, and then a separate institution—such as a local hospital—performs the study and collects the data. This way, the researcher has no ability to influence the results.
That is not what happened with the Nitralis study. DoNotAge paid for the study, did not obtain ethics approval, and ran the study themselves. The sole author—unusual in itself—is an employee of the company that makes the product being evaluated [19].
There is a clear conflict of interest with no separation between trial sponsor and data collection. Under these conditions, the company could publish virtually anything.
To summarize the structural problems so far: a low-quality journal with no impact factor, no ethics approval, and no separation between trial sponsor and data collection. The potential for bias is substantial.
The study itself included 85 participants, randomized to receive either Nitralis or a placebo daily for 30 days [19].
Given the product claims, one would expect the researchers to have measured markers of nitric oxide levels in the blood and included a measure of vascular health.
What they actually assessed was nitrite (with an 'i') in saliva.
The study claims to have measured nitric oxide in the saliva—but that is not what was measured. Nitric oxide is a gas with a half-life of a few seconds. It appears, signals to a cell, and vanishes almost instantly. A gas cannot be captured on a dry paper strip in the mouth.
Every commercial "nitric oxide test strip" on the market is chemically a nitrite test [20].
Here is why this matters. When dietary nitrate from beets is consumed, the digestive system absorbs the nitrate (with an 'a') into the bloodstream. The salivary glands then extract about 25% of that blood nitrate, concentrating it in saliva where bacteria convert it to nitrite (with an 'i'). That is what the saliva test strips are measuring.
The critical problem: an investigation found there was no correlation between higher saliva nitrite levels and elevated nitrite in the blood [20]. In other words, having more nitrite in your mouth does not mean more nitric oxide is being produced in your cardiovascular system.
It is the nitrite in the blood that gets converted into nitric oxide—not the nitrite sitting in saliva.
This study therefore demonstrates only one thing: that participants consuming Nitralis were ingesting more nitrate, which bacteria in the mouth converted to nitrite. The saliva test strips picked up this oral nitrite. There is no measure of blood nitrite levels—the actual endpoint that matters for cardiovascular and exercise effects.
The problems continue. There are no measurements of vascular health whatsoever. Blood pressure was not even measured—a remarkable omission for a product making vascular claims. Blood pressure measurement is non-invasive, inexpensive, and directly relevant. One has to wonder: was the decision to avoid measuring blood pressure deliberate—opting instead for a meaningless outcome that was essentially guaranteed to show a positive result?
This study is essentially worthless as evidence. The claim that Nitralis is "clinically proven to boost nitric oxide levels and vascular performance" is without scientific foundation.
The study functions solely as a marketing tool to claim "Nitralis participants showed a mean +226% increase in NO levels" [19]—which the study does not actually demonstrate.
There is one more problem: the ingredients themselves. The primary ingredient is fermented beet. The fermentation process is intended to increase bioavailability [21].
But does fermentation affect nitrate levels? The evidence here is thin. A patent for one fermentation method claims to yield a beetroot powder with a nitrate content of 7.5% [21].
That would be very high. Normal beetroot powder contains approximately 1.4% nitrate by weight [22].
The Nitralis packaging does not disclose the nitrate content. But being generous and assuming the higher 7.5% concentration: the total Nitralis dose is 800 mg, though not all of it is fermented beet—the exact proportion is not disclosed. If all 800 mg were fermented beet at 7.5% nitrate, that would give a maximum of 60 mg of nitrate per serving.
This is dramatically lower than doses used in clinical trials demonstrating benefits. The heart failure study used 380 mg of nitrate daily [17]. The blood pressure study used approximately 397 mg [16].
Nitralis, at a generous estimate of 60 mg, delivers approximately 15% of the doses used in properly conducted clinical trials—and that is the best-case calculation.
Given this underdosing, it becomes easier to understand why the DoNotAge study measured saliva nitrite rather than blood nitrite. A dose this small may simply not have produced a detectable change in blood nitrite levels.
Practical Recommendations
Nitralis is one example, but it illustrates how easily sound clinical findings can fail to translate into effective supplements—and how easy it is for consumers to spend money on products that cannot deliver on their claims.
For those who want to support nitric oxide levels through evidence-backed means, the most reliable approach is to increase dietary intake of nitrate-rich vegetables. These include beets, spinach, bok choy, rocket (arugula), and other leafy greens [22]. These whole foods deliver nitrate in a food matrix alongside other beneficial nutrients—fibre, polyphenols, potassium—that supplements cannot replicate.
Whole foods consistently outperform supplements in this area. The nitrate content of natural sources is substantial. One study used a bowl of spinach soup as a nitrate source—that single bowl contained 845 mg of nitrate. Nitralis, at best, delivers 60 mg [23].
For those who want to try a beetroot supplement, nitrate content is the single most critical variable—and the supplement industry's track record here is poor. Testing company ConsumerLab found that among the products they tested, nitrate content ranged from as much as approximately 500 mg to as little as 4.3 mg per serving [24]—a more than 100-fold difference between the best and worst products. Without independent third-party testing data, there is no reliable way to know which category a product falls into. A ConsumerLab subscription provides access to these independent testing results and can help narrow selection to products that have actually been verified.
An analysis of 24 beetroot products found that only 5 contained a nitrate level of at least 300 mg per serving—a level considered the minimum threshold to have meaningful health effects [15]. That means the majority of products on the market—19 out of 24 analyzed—fell below the minimum clinically relevant dose.
Those products were:
- Lakewood Organic Beet Juice
- Knudsen Beet Juice
- Beet It Beet Juice
- Beet It Sport Pro Elite Beet Juice
- Beet It Organic Beetroot Shot
Notice that all five are drinks. A capsule cannot carry enough nitrate to make a clinically meaningful difference.
For those looking to support blood pressure naturally, nitrate-rich foods are one evidence-backed tool. Exercise is another. Research has identified specific types of exercise—including forms that can be done at home—that are particularly effective at supporting healthy blood pressure levels.
References
1. https://pmc.ncbi.nlm.nih.gov/articles/PMC122975/
2. https://www.mdpi.com/1422-0067/24/20/15200
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC11504650
4. https://pmc.ncbi.nlm.nih.gov/articles/PMC8348219
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC14594
6. https://pmc.ncbi.nlm.nih.gov/articles/PMC4752190
7. https://pmc.ncbi.nlm.nih.gov/articles/PMC9190231
8. https://pubmed.ncbi.nlm.nih.gov/18708287/
9. https://jn.nutrition.org/article/S0022-3166%2822%2902486-5/fulltext
10. https://journals.physiology.org/doi/abs/10.1152/japplphysiol.00503.2010
11. https://pmc.ncbi.nlm.nih.gov/articles/PMC2291275/
12. https://www.frontiersin.org/articles/10.3389/fspor.2025.1627743/full
13. https://pmc.ncbi.nlm.nih.gov/articles/PMC6369322/
15. https://pmc.ncbi.nlm.nih.gov/articles/PMC8512783/
16. https://pmc.ncbi.nlm.nih.gov/articles/PMC4288952/
17. https://pmc.ncbi.nlm.nih.gov/articles/PMC4892939/
18. https://pubmed.ncbi.nlm.nih.gov/29617153/
19. https://biomedres.us/fulltexts/BJSTR.MS.ID.009914.php
20. https://pmc.ncbi.nlm.nih.gov/articles/PMC5569892/
21. https://patents.google.com/patent/US10702796B2/en
22. https://pmc.ncbi.nlm.nih.gov/articles/PMC10271341/
23. https://pmc.ncbi.nlm.nih.gov/articles/PMC4525132/
24. https://www.consumerlab.com/reviews/beetroot-nitrate-juice-powder-chew/beetroot/
