The pre-workout market has turned nitric oxide into a visual promise: more vasodilation, more pump, more oxygen and, by extension, more performance.
The sequence seems logical. The problem is with the last arrow.
A supplement can increase arginine, nitrate, nitrite or any marker associated with nitric oxide signaling without producing relevant improvements in time, power, sprint repetition or recovery. The mechanism opens up a possibility. It does not deliver the result alone.
This distinction changes the question. Instead of looking for the product that “increases NO the most”, we need to understand which pathway is being stimulated, which outcome really matters and whether the effect appears in the context of the athlete.
Nitric oxide is a message, not a fuel
Nitric oxide, or NO, is a gaseous signaling molecule produced in the body itself. It exists for a short time, acts close to the place where it was formed and participates in different functions depending on the tissue, concentration and metabolic environment.
In vessels, NO activates soluble guanylate cyclase and increases cGMP, favoring the relaxation of smooth muscles and the regulation of vascular tone. In skeletal muscle, it participates in signaling related to calcium handling, contractile function and mitochondrial respiration.
This explains why NO attracts so much interest in performance. It also explains why the phrase “the more the merrier” is inappropriate.
NO does not work like a tank that must be filled to the maximum. In environments of high oxidative stress, its interaction with superoxide can form peroxynitrite and divert signaling towards nitro-oxidative processes. The physiological point is availability in the right place and time, not indiscriminate elevation.
Two routes reach NO by different paths
The arginine and nitric oxide synthase pathway
In the enzymatic route, nitric oxide synthase enzymes, known as NOS, convert L-arginine into NO and L-citrulline. The reaction depends on oxygen and cofactors. In the endothelium, the increase in flow and shear stress caused by exercise activates eNOS and participates in vascular adaptations to training.
This is not just a book engine. In humans, manipulating shear during localized training prevented improvement in endothelial function in the limb in which the stimulus was reduced.
The enterosalivary nitrate pathway
In the second route, dietary nitrate is absorbed, partially returns to saliva and is reduced to nitrite by bacteria in the mouth. After swallowing, nitrite can be converted into NO, especially in regions with less oxygen availability and greater acidity.
This is how leafy greens, beets and standardized sources of nitrate enter the conversation. She also explains why antibacterial rinses can reduce some of the oral conversion. In a crossover trial with people treated for hypertension, three days of antibacterial mouthwash reduced nitrate conversion and slightly raised systolic blood pressure.
How the ideas connect
Increasing a marker is not the same as improving performance
Beetroot, citrulline and arginine can modify steps in the nitric oxide pathway. The biochemical effect, however, does not alone answer whether the athlete will run faster, sustain more power or recover better.
It can increase plasma arginine without guaranteeing vascular or sports improvements.
Can modify nitrate, nitrite and other markers; transfer depends on the task and the athlete.
Time, power, sprints and recovery need to be measured directly.
There are at least three steps between the supplement and what the athlete wants: the compound alters a biochemical marker; the marker modifies a relevant physiological function; This function improves performance on the actual task. Each step needs its own evidence.
Jumping from biomarker to performance is the shortcut used by much of the “NO booster” marketing. The plausibility of the mechanism does not replace a measured sporting outcome.
Measuring more NO is harder than it seems
Because NO is very reactive and short-lived, research generally uses indirect measures: nitrate, nitrite, nitrosothiols, cGMP, urinary excretion, or vascular responses. These indicators are not equivalent and can be influenced by diet, collection, biological compartment and analytical method.
A classic essay helps you see the limitation. In 20 healthy adults, L-citrulline raised plasma arginine more efficiently than oral arginine and increased urinary nitrate and cGMP. Still, no treatment improved flow-mediated dilation.
In 2024, another study compared different markers after nitrate-rich beetroot juice. Plasma nitrite — the most used marker — was not the one that best correlated with pressure changes. Nitrosothiols in whole blood and nitrate in muscle showed closer relationships with the effects evaluated. The study had only 12 participants: it opens an important hypothesis without closing the question.
Biomarker confirms that a pathway has been touched; does not confirm that the athlete got better.
From concept to decision
Beetroot, citrulline and arginine do not occupy the same place
Nitrate and beet juice
Among the nutritional strategies linked to NO, nitrate has the best studied connection with exercise outcomes. A 2025 umbrella review brought together 20 systematic reviews, 180 primary studies, and 2,672 unique participants. There was a favorable signal for time to exhaustion, total distance, muscular endurance, peak power and time to peak — but not for most other outcomes. Eighteen of the 20 reviews were rated as low or critically low quality.
A 2026 meta-analysis also found small to moderate effects of beet juice on sprint interval, average power, and VO₂max. The authors themselves recognized that modality, training status, brand, dose and timing can modify the response.
There is an ergogenic signal, but it is task specific and less predictable in the individual. To delve deeper into dose, timing and field testing, read the review on beet juice and performance.
Citrulline and citrulline malate
Citrulline bypasses part of the pre-systemic elimination of arginine and manages to increase the plasma availability of this amino acid. This makes the mechanism plausible and, pharmacokinetically, more interesting than simply ingesting arginine.
Performance is yet another question. A 2026 meta-analysis gathered 30 randomized trials, 644 participants, and 138 effect sizes. Citrulline malate was associated with a small improvement in overall performance, with g of 0.16. Prediction intervals were wide, certainty varied from low to very low and dose, timing and target audience remained without reliable definition.
For endurance, a previous meta-analysis with ten studies found no significant benefit on performance, perceived exertion, VO₂ kinetics or lactate.
Arginine
Arginine is the direct substrate of NOS, but its oral supplementation suffers from intestinal and hepatic metabolism before reaching the circulation. Performance reviews have produced heterogeneous results, often with small studies, different protocols and greater risk of bias.
Therefore, “direct substrate” does not mean “best supplement”. For many athletes, arginine also has less favorable gastrointestinal tolerance at high doses. A systematic review found little performance gain and noted the possibility of gastrointestinal and cardiovascular effects in the short term.
Vascular health and performance are not the same outcome
The interest in NO goes beyond sport. A dose–response meta-analysis published in 2025 brought together 75 randomized trials and 1,823 participants. Dietary nitrate increased plasma nitrate and nitrite and was associated with small mean pressure reductions, in addition to improvements in some vascular markers.
This does not authorize replacing hypertension treatment with juice, powder or capsule. It also does not allow us to assume that a pressure reduction automatically improves performance. In those who already have low blood pressure, the same effect can increase dizziness or discomfort.
The right outcome depends on the objective. For vascular health, pressure, endothelial function and clinical monitoring are important. For performance, the test needs to connect to competitive demand.
The central shift
How to turn the engine into a better decision
Before using a resource aimed at NO, go through five questions.
- Which outcome should change?Set time, power, distance, sprint repetition, muscular endurance or blood pressure. Feel more pump It is not synonymous with competitive improvement or chronic hypertrophy.
- Does the chosen path fit the task?Nitrate has better support for some endurance outcomes, intermittent efforts and muscle function. Citrulline malate may produce small gains in some tests; Arginine alone is less predictable.
- Is the protocol measurable?Product, dose, time, previous meal and training context need to be repeatable. For nitrate, milliliters are not enough: it is necessary to know the effective quantity.
- Does the test measure what matters?Repeat comparable sessions and record main outcome, tolerance and perceived exertion. If the marker changes but the task does not, the marker should not win the decision.
- Is there a clinical context that changes safety?Low blood pressure, dizziness, cardiovascular disease and vasoactive medications require individual guidance. Prescribed mouthwash should not be discontinued on its own.
The most obvious supplement is not the first step
Regular training repeatedly increases flow and shear on the endothelium. Vegetables rich in nitrate can be part of a high-quality diet. Sleep, energy availability, carbohydrates, hydration and load organization continue to determine a much larger portion of performance.
The supplement starts to make sense when it comes after these fundamentals and answers a concrete question.
Also read about mitochondria and energy production, weekly load in football and the proposal of Rafa Barleze Community.
Nitric oxide deserves attention because it connects vessels, muscles and metabolism. It deserves skepticism because marketing often turns this connection into a promise.
The most useful question is not “how to maximize NO?” It's another:
For this athlete, in this task, in this way, does the physiological effect become a result worth maintaining?
Frequently asked questions
More pump Does it mean more hypertrophy?
Not necessarily. O pump reflects acute changes in flow, cell volume and metabolite accumulation. It can accompany a good session, but it does not directly measure mechanical tension, effective volume or chronic muscle mass gain.
Is citrulline better than arginine?
To raise plasma arginine, citrulline is usually more efficient as it undergoes less pre-systemic elimination. This does not guarantee superior performance. The evidence for citrulline malate points to, at best, a small and context-dependent effect.
Does beetroot work for all athletes?
No. Beet nitrate has a favorable signal in specific outcomes, but the response varies with modality, training level, dose, timing and individual. Use should be tested in comparable sessions prior to competition.
Does mouthwash cancel the effect of nitrate?
Antibacterial rinses can reduce the oral conversion of nitrate to nitrite and weaken the enterosalivary pathway. This is not a reason to forgo necessary dental care; the protocol must be adjusted with discretion.