Nitric oxide levels fall with age — and this decline is linked to an array of age-related problems in areas like heart, brain, reproductive, and muscle health [1][2]. Cue predatory supplement brands that try to take your money by spinning a story that their pill will stop this decline.
But there's an alternative. There's a cheap and incredibly effective nitric oxide booster that I take, and it doesn't line the pockets of supplement companies.
Table of Contents
- Why You Can't Just Swallow Nitric Oxide
- The Supplement Approach: L-Arginine and L-Citrulline
- The Nitrate Pathway: Beetroot Juice
- Tadalafil: A Different Kind of NO Booster
- The Nitric Oxide Booster I Actually Take
- References
Why You Can't Just Swallow Nitric Oxide
Notice I said nitric oxide booster. Nitric oxide itself is an incredibly unstable gas. We can't just swallow it. So we need to find other strategies to raise nitric oxide levels in our blood vessels. The intravascular half-life of nitric oxide is approximately 2 milliseconds [3] — it's gone almost as soon as it's made.
Pharmaceutical manufacturers solved this problem 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 [4]. 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.
So the supplements you'll find on the market take a different approach. Instead of bypassing the body's natural pathway of nitric oxide production, they are intended to support it. They are, in essence, trying to supply more of the raw materials out of which the body creates nitric oxide.
But it hasn't been easy.
The Supplement Approach: L-Arginine and L-Citrulline
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 [5].
Many human studies have looked at L-arginine supplements [6][7][8]. And while L-arginine levels in the blood go up, that hasn't reliably translated to athletic performance improvements or raised nitric oxide levels.
That's where another option, 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 [9]. 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 [10].
However, a 2019 meta-analysis did find that L-citrulline seems to slightly reduce blood pressure, when the dose was at least 6 g/day [11]. Not really much to get excited about.
But more recently, the excitement has been building about nitrate supplements. They target a recently discovered pathway for supplying nitric oxide to our cells.
The Nitrate Pathway: Beetroot Juice
Now pay attention, because this matters in terms of what type of supplement you may want to choose.
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 produce nitric oxide in the blood [12]. A popular type of supplement in this category is derived from beets, since they are rich in nitrate [13].
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 [14].
The study found that beetroot juice supplementation significantly reduced blood pressure by around 8 points. Amazingly, this effect size is comparable to the impact of blood pressure medication — a meaningful amount for reducing the risk of things like strokes and heart attacks [14]. The study also found that the beetroot juice supplement improved blood vessel function by about 20% and reduced arterial stiffness [14].
Another study found just a week of daily doses of beetroot juice containing 378 mg of nitrate significantly improved exercise endurance and blood pressure in elderly patients with heart failure [15].
But here's where we really need to be cautious. Beetroot products are all over the map when it comes to nitrate levels. 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 — more than a 100-fold difference [16].
Supplements with beetroot powder were particularly liable to have lower nitrate levels. Another analysis of 24 beetroot products found only 5 contained a nitrate level of at least 300 mg per serving — a level considered a minimum to have actual health effects [13].
You can't get that amount of nitrate from a pill. So any supplement company selling you a pill "nitric oxide booster" is essentially taking your money for nothing meaningful.
Instead, to reach that 300 mg dose, you need a product like beet juice. And obviously, you could just eat beets. Generally, it's ideal when we can get nutrients we're targeting in their natural, whole-food form, because we get all the other nutrients contained in that food as well.
But beets have a downside. They are one of the highest food sources of oxalate [17]. Oxalate can inhibit the bioavailability of certain nutrients by binding to minerals and reducing their absorption [18]. And it can lead to kidney stones, particularly for susceptible individuals [17].
Tadalafil: A Different Kind of NO Booster
There's another option I want to explore. Interestingly, there's an off-patent — which means it's cheap — pharma drug that may address this nitric oxide issue called tadalafil. And while I don't take it currently (I take a different nitric oxide booster instead), I may start taking tadalafil in the future as more data comes out.
The medication was originally researched as a treatment for cardiovascular diseases such as hypertension and angina. The way it works is interesting. Instead of trying to add nitrate from the outside, it essentially amplifies the signal the nitric oxide in the body is already sending.
Here's how it works. Nitric oxide relaxes blood vessels by creating a messenger molecule called cGMP. But your body produces an enzyme called PDE5 that destroys cGMP almost as fast as it's made. Tadalafil works by blocking PDE5. By stopping the breakdown of cGMP, tadalafil amplifies and prolongs the effects of the nitric oxide your body is already producing [19].
And it's been growing in popularity because it's been linked to some eye-catching mortality-related data. A recent study looked at a massive database of health records to track the health outcomes for men prescribed tadalafil — or a similar medication — over 3 years. Compared to those not taking this class of medication, tadalafil was associated with a 34% risk reduction for death and a 27% reduction for heart attacks. Stroke risk was 34% lower, and dementia risk fell by 32% [20].
A 2024 U.K. Biobank study turned up similar data. Tadalafil was associated with a 28% reduced risk of death from all causes [21].
But we need to be really cautious here. These are observational studies. The data is intriguing, but there's a serious potential for healthy user bias skewing the results. Tadalafil is most often prescribed for erectile dysfunction. Men who are prescribed tadalafil and continue taking it are, almost by definition, healthier than men with ED who aren't treated. They're also engaged with the healthcare system, likely have better baseline cardiovascular function, and may have healthier lifestyles overall. We just don't know what's going on for sure until we have data from randomized controlled trials. That data isn't there yet.
And it's worth mentioning that no current guidelines recommend tadalafil for preventive cardiovascular care.
Moreover, there are important contraindications. Tadalafil can be dangerous for patients who are taking nitrate medications like nitroglycerin or ISMN — the combination can lead to a life-threatening drop in blood pressure [19].
Plus, the actual impact of tadalafil on blood pressure is minimal — less than 1.5 mmHg and often less than 1.0 mmHg compared to placebo [22]. And blood pressure is the area that many people who are looking at nitric oxide boosters are most interested in.
For me, we need randomized controlled trial data. The observational data, while interesting, has far too much potential for confounding, and we can't prove causation.
The Nitric Oxide Booster I Actually Take
Which brings us to the nitric oxide booster I actually take.
It's a natural food source of nitrates, just like beets. But unlike beets, it's low in oxalate [18].
It's actually one of the highest nitrate vegetables available, comfortably surpassing beets on average. A worldwide systematic review and meta-analysis of nitrate in vegetables found that rocket (arugula) contains approximately 4,825 mg of nitrate per kg — compared to about 3,000 mg/kg for beetroot [23].
So what's the vegetable? Arugula — or rocket. An arugula salad is an evidence-backed, zero-risk, whole-foods-based approach to getting a significant dose of dietary nitrate.
Let me quickly run through the numbers. At about 4.8 mg of nitrate per gram of arugula, if we want to hit that 300 mg level mentioned earlier, that's a salad of about 63 grams.
A delicious, simple way to prepare an arugula salad is just arugula plus olive oil, pepper, and lemon juice.
And it doesn't line the pockets of supplement companies or pharma.
References
1. https://pmc.ncbi.nlm.nih.gov/articles/PMC11504650
2. https://pmc.ncbi.nlm.nih.gov/articles/PMC8348219/
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC14594
4. https://pmc.ncbi.nlm.nih.gov/articles/PMC4752190
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC9190231/
6. https://pubmed.ncbi.nlm.nih.gov/18708287/
7. https://jn.nutrition.org/article/S0022-3166%2822%2902486-5/fulltext
8. https://journals.physiology.org/doi/abs/10.1152/japplphysiol.00503.2010
9. https://pmc.ncbi.nlm.nih.gov/articles/PMC2291275/
11. https://pmc.ncbi.nlm.nih.gov/articles/PMC6369322/
13. https://pmc.ncbi.nlm.nih.gov/articles/PMC8512783/
14. https://pmc.ncbi.nlm.nih.gov/articles/PMC4288952/
15. https://pmc.ncbi.nlm.nih.gov/articles/PMC4892939/
16. https://www.consumerlab.com/reviews/beetroot-nitrate-juice-powder-chew/beetroot/
17. https://www.imrpress.com/journal/FBL/8/6/10.2741/1082
18. https://pmc.ncbi.nlm.nih.gov/articles/PMC10486698/
19. https://www.ncbi.nlm.nih.gov/books/NBK603743/
20. https://www.amjmed.com/article/S0002-9343(24)00705-8/fulltext
21. https://onlinelibrary.wiley.com/doi/10.1111/acel.14334
22. https://pmc.ncbi.nlm.nih.gov/articles/PMC8845471/
23. https://www.sciencedirect.com/science/article/pii/S0147651323004384
