Citrulline or Beetroot Nitrates: What's the Difference

Citrulline and beetroot juice are called "NO boosters," but they reach nitric oxide by different biochemical roads. The editorial team explains what the difference in mechanisms is, what the research says, and why mouthwash can nullify the effect of beetroot juice.

A shared goal - nitric oxide

Both citrulline and nitrates from beetroot are sold as "NO boosters" - agents for raising the level of nitric oxide (NO). This molecule dilates blood vessels and affects blood flow in the muscles, the contractility of muscle fibers and the work of mitochondria. However, a shared endpoint does not mean identical physiology: these substances reach NO by different roads.

Citrulline is a non-essential amino acid that is not part of proteins. Its name comes from the Latin name for watermelon (Citrullus), where it was first discovered. In sports nutrition citrulline is found in two forms: pure L-citrulline and citrulline malate - a compound with malic acid.

Nitrates are inorganic anions NO₃⁻, which are contained in significant amounts in beetroot, arugula, spinach, celery and other leafy vegetables. In sports products they are usually presented as concentrated beetroot juice or a powder with a standardized nitrate content.

On the surface both products promise a "pump" and endurance, but their mechanisms, duration of action and evidence base differ substantially. Our breakdown is precisely about these differences.

Two biochemical pathways

Citrulline works through the classic NO synthase pathway. After absorption it is converted in the kidneys into L-arginine, and arginine is the substrate for the enzyme NO synthase. This enzyme requires oxygen, so the pathway is most efficient in well-oxygenated tissues.

Interestingly, citrulline raises plasma arginine levels more effectively than arginine itself. This was shown, in particular, by Schwedhelm and colleagues in a 2008 pharmacokinetic study: oral arginine is largely broken down in the gut and liver, whereas citrulline bypasses this "barrier."

Nitrates take an alternative pathway. After absorption, part of the nitrate returns with saliva to the oral cavity, where bacteria on the back of the tongue reduce it to nitrite. The nitrite is swallowed, absorbed and, in the tissues, converted into NO - and this process is enhanced precisely under the conditions of hypoxia and acidification characteristic of a working muscle.

An important practical nuance follows from this: antibacterial mouthwashes suppress the oral microflora and significantly reduce the effect of nitrates. This factor does not affect citrulline.

What the research shows

Nitrates have a stronger evidence base. As early as 2007 Larsen and colleagues showed a reduction in the oxygen "cost" of exercise after taking sodium nitrate, and in 2009 Bailey's group reproduced the effect with beetroot juice. The 2018 IOC consensus classes nitrates among supplements with good evidence of effectiveness.

The main effect of nitrates is improved economy: the same pace requires less oxygen. Senefeld's 2020 meta-analysis confirmed a small but statistically significant ergogenic effect, most noticeable in less-trained and amateur athletes. In elite endurance athletes the effect is often weaker.

For citrulline the results are more mixed. Some studies, such as the 2010 work by Perez-Guisado and Jakeman with 8 g of citrulline malate, showed more repetitions in strength training and less muscle soreness. However, the 2020 review by Gonzalez and Trexler notes the inconsistency of the data and the small effect sizes.

Another problem with citrulline research is that different forms are studied. Citrulline malate contains malic acid, which may itself affect energy metabolism, and the ratio of citrulline to malate in products varies. This makes it hard to compare results directly.

Comparison of key characteristics

For clarity the editorial team brought the main differences together in a table. The doses given are those used in studies.

The difference in timing is related to pharmacokinetics: the plasma nitrite level peaks about 2-3 hours after taking nitrate, because the enterosalivary cycle has to run its course. Citrulline is absorbed and converted into arginine faster.

The "areas of specialization" also differ. Nitrates are best studied in cyclic sports: running, rowing, cycling, as well as in repeated intense efforts. Citrulline has more often been studied in strength training with a high number of repetitions.

Finally, neither substance is banned by WADA. However, as with any supplement, product certification matters for athletes who undergo testing.

Safety and side effects

Citrulline is well tolerated at the doses studied. In some people gastrointestinal discomfort is possible, although it occurs less often than with arginine. People who take nitrates to treat the heart or PDE-5 inhibitors should clear any "NO boosters" with a doctor because of the risk of an excessive drop in blood pressure.

Beetroot juice is also safe for most people, but has characteristic features: red coloring of the urine (beeturia) and stool, which alarms the unprepared. This is harmless. People prone to oxalate kidney stones should remember that beetroot is rich in oxalates.

A separate issue is nitrosamines. Historically, nitrates in food were linked to a risk of forming carcinogenic compounds, but this risk mainly concerns nitrites in processed meat. Nitrates from vegetables come together with antioxidants (vitamin C, polyphenols) that inhibit nitrosation.

• Do not combine supplements with prescription nitrates and sildenafil without a doctor.
• Do not use antiseptic mouthwashes on the day you take nitrates.
• Do not be alarmed by pink urine after beetroot juice.

Editorial conclusions

Citrulline and beetroot nitrates lead to nitric oxide by different pathways: the first through arginine and the oxygen-dependent NO synthase, the second through nitrite, and this pathway is enhanced precisely under conditions of oxygen shortage.

Nitrates have a stronger evidence base, especially regarding economy and endurance. The data on citrulline are more contradictory and concern mainly strength training with a high number of repetitions.

Both substances are safe for most healthy people, but require caution in the case of taking cardiac nitrates or medications for potency.

On this topic the editorial team also recommends our materials on arginine and its bioavailability, on caffeine for endurance, and on how to assess the quality of pre-workout complexes.

References

1. Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008;7(2):156–167.
2. Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51–59.
3. Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxf). 2007;191(1):59–66.
4. Bailey SJ, Winyard P, Vanhatalo A, et al. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol. 2009;107(4):1144–1155.
5. Jones AM. Dietary nitrate supplementation and exercise performance. Sports Med. 2014;44(Suppl 1):S35–S45.
6. Senefeld JW, Wiggins CC, Regimbal RJ, et al. Ergogenic effect of nitrate supplementation: a systematic review and meta-analysis. Med Sci Sports Exerc. 2020;52(10):2250–2261.
7. Gonzalez AM, Trexler ET. Effects of citrulline supplementation on exercise performance in humans: a review of the current literature. J Strength Cond Res. 2020;34(5):1480–1495.
8. Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. 2010;24(5):1215–1222.