I honestly can't believe what I've just read.
I was going through the nitric oxide supplement literature, and it’s a lot more promising than I’d thought before starting my review—especially since nitric oxide levels decline with age.
Then I started looking for a good brand, and I came across Nitralis from a company called DoNotAge. The more I looked, the worse it got.
In this article, I’ll break down the research so that if you decide to start taking nitric oxide supplements, you don’t get duped by marketing hype—and you can select a good brand. I’m not affiliated with any nitric oxide supplement brand.
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 got better during the week, but then returned to normal on the weekend. It was the nitroglycerin they were exposed to. Doctors realized it caused their blood vessels to relax, opening them wider and relieving pressure [1].
But we didn’t discover the mechanism until the 1970s. It was caused by nitric oxide, which is produced as the nitroglycerin is broken down. Nitric oxide relaxes the smooth muscle cells that line blood vessel walls [1].
And we soon learned, during the 1980s, that nitric oxide was 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 as well [2].
This emerging understanding of nitric oxide stimulated interest among supplement makers. They wondered how we might boost levels as an aid for athletic performance—not just for heart problems. Increasing blood flow could enhance oxygen and nutrient delivery, leading to peak performance and a greater impact from exercise.
And there’s another factor that adds urgency to this area. The problem is that our bodies’ ability to produce nitric oxide declines with age [3].
And 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].
But even if we can see a potential benefit for increasing nitric oxide levels, there’s a challenge we need to overcome. We can’t just swallow nitric oxide. It’s an extremely unstable gas. And in the body, it reacts immediately with other substances. It’s gone almost immediately [5].
This problem was actually solved by pharmaceutical manufacturers a while ago. In the clinic, I prescribe medications like GTN sprays and ISMN that result in the production of nitric oxide where it’s needed in the body. But these are prescription medications.
Moreover, there’s an Achilles’ heel with medications like ISMN. When patients are taking them, the body rapidly builds tolerance, and they lose much of their effectiveness [6].
That’s because of the way these drugs work. They don’t 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 the outside, they asked: What if we could support the body’s built-in nitric oxide pathway itself?
That way, we could take something long-term that doesn’t lose its effect, and that may help counter the natural decline in nitric oxide production that comes with age. In that sense, it’s not a drug substitute—it’s a tool that may help support one of the systems linked to healthy aging.
Supplements
The logic makes sense. But how has it worked out in the supplement space? Let’s take a look at the main strategies supplement manufacturers have used to enhance nitric oxide production and see what the research says.
When you look at nitric oxide supplements—often called “nitric oxide boosters”—the most common ingredient you’re likely to see is L-arginine. It’s an amino acid that’s a key ingredient of the primary pathway for nitric oxide production in the body [7].
Many human studies have looked at 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]
And while L-arginine levels in the blood go up, that hasn’t reliably translated to athletic performance improvements or raised nitric oxide levels.
But that’s where L-citrulline comes in. It gets converted to L-arginine after ingestion. Research has shown it’s actually more effective than L-arginine itself in raising blood levels of L-arginine [11]. So maybe L-citrulline would be able to raise nitric oxide levels, where L-arginine failed?
Unfortunately, the research has been underwhelming here, too, when it comes to performance. For example, a study last year tested L-citrulline in healthy young adults to see if it would increase time to exhaustion during exercise. It didn’t [12].
However, a 2019 meta-analysis did find that L-citrulline seems to slightly reduce blood pressure, when the dose was at least 6g/day. Not really much to get excited about [13].
But more recently, the excitement has been building about nitrate supplements. They target a recently discovered pathway for supplying nitric oxide to our cells.
Nitrate, with an ‘a’, found naturally in foods like leafy greens, is converted into nitrite, with an ‘i’, by bacteria on the tongue and further modified through digestion to eventually lead to nitric oxide in the blood [14].
A popular type of supplement in this category is derived from beets, since they are rich in nitrate [15].
Do supplements targeting this pathway actually work? In clinical trials, results have been encouraging. An important study in 2014 tested the effects of a daily dose of beetroot juice containing about 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.
Amazing, this effect size is comparable to the impact of blood pressure medication. It’s a meaningful amount for reducing the risk of things like strokes and heart attacks [16].
The study found the beetroot juice supplement also improved blood vessel function and stiffness [16].
Another study found just a 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
But here’s where we need to be cautious. Just because a substance is helpful in a clinical trial doesn’t mean supplement companies are going to use it properly in their products. And I want to look at one example that demonstrates just how bad it can get, so that you know what to look out for when selecting a nitrate supplement brand.
The product is called Nitralis from DoNotAge. It’s based on the nitrate pathway we’ve been discussing, with fermented beet as the primary ingredient [19].
If you have a look at their website, you’ll see a set of four claims. Nitralis supposedly:
- Is clinically proven to boost nitric oxide levels and vascular performance
- Boosts circulation and vascular health
- Enhances physical performance
- Supports cognitive function [19]
We’ve already looked at research that shows 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 in the brain should help with certain aspects of our brain’s functioning. It makes sense. But the 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].
So there’s a big question mark with that particular benefit. Not the end of the world. Supplement companies often stretch the truth. But it gets so much worse.
Let’s come back to the impacts on blood flow, vascular health, and endurance. We’ve seen clinical trial evidence that a nitrate supplement based on beets can help. But what about this particular supplement?
Notice a key claim for Nitralis. It’s “clinically proven to boost nitric oxide levels and vascular performance.” Great. So there’s a clinical trial. Let’s have a look at it [19].
The clinical trial in question was published in the Biomedical Journal of Scientific & Technical Research [19].
Before diving into the study itself, it’s worth pointing out a couple red flags. First, the article was received on October 3 and published just 2 weeks later. This is an incredibly fast turnaround for a scientific journal. The peer-review process usually takes much longer, suggesting a journal more interested in pumping out papers than ensuring quality. The journal itself doesn’t even have an impact factor.
Then, notice the institutional affiliation listed: DoNotAge.org, described as a Health Research Organization. That’s a bit of a stretch. It’s just a supplements company.
Now when supplement or pharma companies sponsor clinical trials, there should be a wall between the sponsor and whoever actually performs the trial.
Take my Rapamycin and Exercise clinical trial, for example. I wrote the trial protocol, applied for and received ethics permission, and crowdfunded the study. But a local hospital in Auckland, New Zealand performed the study and collected the data. This way, I didn’t have any ability to sway the results.
That’s not what happened with this Nitralis study. They paid for the study, didn’t get ethics approval, and ran the study themselves. And the sole author (and having just one is also unusual) is an employee of the company that makes the product being evaluated [19].
So there’s a clear conflict of interest and no separation between the trial sponsor and the data collection. DoNotAge could publish literally anything.
So far then: trash journal, no ethics approval, no separation between trial sponsor and data collection. Huge potential for conflicts of interest.
Now let’s dive into the study itself. It included 85 participants, randomized to receive either Nitralis or a placebo daily for 30 days [19].
What were they looking for? Given the claims on the product page, you’d expect they checked for markers of nitric oxide levels in the blood and included a measure of vascular health.
But here’s what they actually assessed: nitrite, with an ‘i’, in saliva.
They say they measured nitric oxide in the saliva. That’s not what they measured. Remember, nitric oxide is a gas with a half-life of a few seconds. It appears, signals to a cell, and vanishes almost instantly. You cannot capture a gas on a dry paper strip in your mouth.
Every commercial "nitric oxide test strip" on the market is chemically a nitrite test [20].
Let me explain why this is deceptive.
When you eat some nitrate from beets, for example, your digestive system absorbs the nitrate with an ‘a’. That goes into your bloodstream. The salivary glands then extract about 25% of that blood nitrate, concentrating it in your saliva where bacteria convert it to nitrite with an ‘i’. That’s what the saliva test strips are measuring.
Here’s the problem. An investigation found that there was no correlation between having higher saliva nitrite levels and elevated nitrite in the blood [20].
And it’s the nitrite in the blood that gets converted into nitric oxide.
So this study basically shows just one thing: that participants consuming Nitralis got more nitrate with an ‘a’, which was then converted by the bacteria in the mouth to nitrite with an ‘i’. But there’s no measure of blood nitrite levels. That’s the whole point, which they’ve missed.
And it continues to get worse.
There are no measurements related to vascular health. They didn’t even measure blood pressure, which is a mindboggling omission. It’s non-invasive, cheap, and highly relevant here. I can’t help but wonder: Did they deliberately choose to avoid measuring an endpoint where the product might fail, opting instead for a meaningless outcome that was basically guaranteed to show a positive result?
So this study is basically worthless. The claim that Nitralis is “clinically proven to boost nitric oxide levels and vascular performance” is ungrounded.
This ‘study’ is solely a marketing gimmick to say “Nitralis participants showed a mean +226% increase in NO levels” [19]. Which it absolutely does not.
Here’s the worst part, though. The ingredients. Consider the star of the show — beets. The form they use here is fermented beet. The fermentation process is intended to increase bioavailability [21].
Does it also affect nitrate levels? I was unable to find much data here. Though a patent for a fermentation method claims to yield a beetroot powder with a nitrate content of 7.5% [21].
That would be really high. According to one source, normal beetroot powder would be about 1.4% nitrate by weight [22].
The Nitralis packaging doesn’t tell us, but let’s be generous and assume that higher concentration of 7.5%. The dose for Nitralis is 800 mg, but not all of this is fermented beet. How much is? Again, we’re not told. But suppose all 800 mg were. That would give us up to 60 mg of nitrate.
This is a much, much smaller dose than is used in the clinical studies we’ve looked at showing benefits for heart failure and blood pressure. The older adults with heart failure, for instance, got 380 mg a day of nitrate [17].
The blood pressure study used around 397 mg of nitrate [16].
So Nitralis from DoNotAge, if it gives 60mg of Nitrate, is about 15% of the doses used in proper clinical trials. And that’s if we’re being generous.
And since it’s such a small dose, I wonder if that’s why DoNotAge wanted to test saliva nitrite levels, rather than blood nitrite levels. A dose this small may not have shown up in the blood.
Practical Recommendations
Nitralis is just one supplement. It shows how easy it is, though, for sound clinical findings to fail to translate into actually helpful supplements. It’s easy to end up wasting your money.
But if we want to boost nitric oxide in our blood, there’s a safe, evidence-backed approach we can take instead. We can increase dietary intake of nitrate-rich vegetables. This includes beets, spinach, bok choy, and others [22].
Whole foods are always better than supplements. If you want the benefits of beets, just eat beets. It’s amazing how much nitrate can be found in natural sources. One study, for instance, used a bowl of soup with spinach in it as a source of nitrate. That bowl contained 845 mg of nitrate. Remember, Nitralis has up to 60 mg [23].
And if you’d like to try a beet root supplement product, it’s critical to ensure you’re getting a quality brand where the nitrate content is adequate. Testing company ConsumerLab found that, in the products they tested, nitrate ranged from as much as about 500 mg to as little as 4.3 mg in a serving [24].
If you’d like to access their testing results, I highly recommend a subscription to ConsumerLab. It’s a fantastic resource to help you pick supplements with confidence. And just to be clear, I’m not affiliated with them in any way.
Another analysis of 24 beet root products found only 5 contained a nitrate level of at least 300 mg per serving. This is a level considered a minimum to have actual health effects [15].
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 they are all drinks. A capsule can’t carry enough nitrate to make a clinically meaningful difference.
And if we’re looking to reduce blood pressure naturally, there’s another important tool we can use in addition to adding more nitrate-rich foods to our diet. Exercise. But some recent research answers a key question: Which kind of exercise can lower blood pressure the most? The answer turns out to be a type of exercise that’s super simple to do at home.
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/
