Nitric oxide (NO) supplements are one of the biggest categories in sports nutrition and cardiovascular health. The marketing promises are bold: better pumps, lower blood pressure, improved circulation, enhanced endurance. Some of these claims have solid research behind them. Others are running way ahead of the evidence.
Here’s the thing: you can’t actually take nitric oxide in a pill. It’s a gas your body produces naturally. Every “nitric oxide supplement” is really a precursor — a molecule your body converts into NO. The question is which precursors actually move the needle, at what doses, and for whom.
How Your Body Makes Nitric Oxide
Understanding NO production explains why some supplements work and others don’t.
Your body has two main pathways for producing nitric oxide:
1. The L-arginine–NOS pathway
The amino acid L-arginine is converted to nitric oxide by a family of enzymes called nitric oxide synthases (NOS). There are three isoforms: endothelial NOS (eNOS) in blood vessel walls, neuronal NOS (nNOS) in nerve tissue, and inducible NOS (iNOS) during immune responses [1].
This pathway is the dominant source of NO in healthy people. L-citrulline enters the picture because the body recycles it back into L-arginine via the kidneys, effectively sustaining arginine availability — sometimes more efficiently than supplementing arginine directly.
2. The nitrate–nitrite–NO pathway
Dietary nitrate (NO₃⁻), found abundantly in beetroot and leafy greens, is reduced to nitrite (NO₂⁻) by bacteria on the tongue, then further converted to NO in the acidic environment of the stomach and in tissues under low-oxygen conditions [2]. This pathway becomes especially important during exercise and in conditions where NOS function is impaired (aging, cardiovascular disease).
Key point: Mouthwash that kills oral bacteria can substantially reduce the nitrate-to-nitrite conversion step, blunting the blood pressure and performance effects of dietary nitrate [3]. This is a well-replicated finding that surprises most people.
The Three Main NO Precursor Supplements
L-Citrulline: The Best-Supported Option
L-citrulline is an amino acid found in watermelon (the name comes from Citrullus, the Latin name for watermelon). It’s converted to L-arginine in the kidneys, raising plasma arginine levels more effectively than supplementing arginine itself — because arginine taken orally gets substantially degraded in the gut and liver (first-pass metabolism) before reaching systemic circulation [4].
What the evidence supports:
- Blood pressure reduction: A 2019 meta-analysis of 15 RCTs found that L-citrulline supplementation significantly reduced systolic blood pressure (−4.1 mmHg) and diastolic blood pressure (−2.1 mmHg), with stronger effects in hypertensive populations [5]. These are modest but clinically meaningful reductions.
- Exercise performance: Results are mixed but lean positive. A 2020 systematic review found that citrulline supplementation (typically 6–8 g) improved high-intensity exercise performance in some studies, particularly for repetitions to failure in resistance training. Endurance benefits were less consistent [6].
- Citrulline malate specifically: Many studies use citrulline malate (citrulline bonded to malic acid) at 6–8 g. A frequently cited 2010 study (Pérez-Guisado & Jakeman) found increased repetitions to failure and reduced muscle soreness with 8 g citrulline malate [7]. However, a 2023 review noted that the malate component may contribute independently to exercise performance, making it hard to isolate citrulline’s effect [8].
Effective doses: 3–6 g/day L-citrulline for blood pressure effects; 6–8 g citrulline malate pre-workout for exercise.
Many of these ingredients also work well as stimulant-free pre-workout options for people who want performance support without caffeine or other stimulants.
What’s overhyped: Claims that citrulline will dramatically transform your workouts. The effects, when present, tend to be modest — a few extra reps, slightly reduced perceived exertion. Meaningful, but not transformative.
→ Full deep-dive: L-Citrulline Supplements — Dosing, Evidence, and What to Expect
L-Arginine: The Original, Now Mostly Superseded
L-arginine was the first NO precursor supplement to gain popularity, largely on the back of the 1998 Nobel Prize for the discovery of nitric oxide’s role in vasodilation.
The bioavailability problem: Oral L-arginine has approximately 20–70% systemic bioavailability, with substantial variability between individuals [9]. Significant amounts are metabolized by arginase in the gut wall and liver before reaching the bloodstream. This is the “arginine paradox” — despite theoretically saturating NOS, supplemental arginine often doesn’t raise NO production proportionally.
What the evidence supports:
- Blood pressure: Some meta-analyses show modest blood pressure reductions (2–5 mmHg systolic). A 2021 meta-analysis of 31 RCTs found significant reductions in both systolic and diastolic BP, but noted high heterogeneity across studies [10].
- Erectile dysfunction: There’s moderate evidence that L-arginine (1.5–5 g/day) may improve mild-to-moderate ED, especially in combination with pycnogenol or citrulline. A 2019 meta-analysis found significant improvement in subjective erectile function scores [11]. Effects are much weaker than PDE5 inhibitors.
- Exercise performance: Evidence is weaker and less consistent than for citrulline. Most recent reviews suggest arginine is inferior to citrulline for this purpose [12].
Effective doses: 3–6 g/day, often split into multiple doses due to GI tolerance.
Why citrulline usually wins: L-citrulline raises plasma arginine more reliably, with fewer GI side effects (arginine at higher doses commonly causes bloating and diarrhea).
→ Full deep-dive: L-Arginine Supplements — The Evidence, Limits, and Better Alternatives
Beetroot / Dietary Nitrate: The Performance Darling
Beetroot juice (and concentrated beetroot supplements) work through the nitrate–nitrite–NO pathway. This is a completely different mechanism from citrulline/arginine, which means the two approaches can theoretically stack.
Curious which ingredient delivers better gym pumps? Our head-to-head comparison of beetroot vs citrulline for pumps breaks down the evidence.
What the evidence supports:
- Exercise performance in endurance sports: This is beetroot’s strongest claim. A landmark 2009 study by Bailey et al. showed that beetroot juice (~6.2 mmol nitrate/day) reduced the oxygen cost of submaximal exercise and extended time to exhaustion by ~16% [13]. Subsequent studies and meta-analyses have confirmed a performance benefit, though typically smaller (1–3%) in well-trained athletes [14].
- Blood pressure: Robust evidence. A 2013 meta-analysis of 16 trials found that inorganic nitrate/beetroot juice reduced systolic BP by ~4.4 mmHg [15]. A larger 2018 meta-analysis confirmed similar findings [16]. Effects are strongest in untreated hypertension and may be blunted in people already on antihypertensives.
- Cognitive function: Emerging but preliminary. Several small trials in older adults suggest that dietary nitrate may improve cerebral blood flow and aspects of cognitive performance, but the evidence base is still early-stage [17].
The elite athlete caveat: Multiple studies show that highly trained endurance athletes (VO₂max > 65 mL/kg/min) are less responsive to nitrate supplementation, possibly because their NOS pathways are already highly optimized [18]. Recreational athletes and older adults tend to see larger benefits.
Effective doses: ~6–12 mmol nitrate/day, typically from ~500 mL beetroot juice or concentrated shots (70 mL shots standardized to ~6.4 mmol). Timing: 2–3 hours before exercise for acute performance effects; chronic loading (3–7 days) may enhance benefits.
What’s overhyped: Marketing that implies beetroot supplements work identically to beetroot juice. Many capsule/powder products don’t standardize to nitrate content, so you may be getting a fraction of the studied dose.
→ Full deep-dive: Beetroot and Nitrate Supplements — Performance, Blood Pressure, and Dosing
Claims That Need Honest Context
“Nitric oxide supplements improve circulation”
Partially supported. NO is a vasodilator, and increasing NO production can improve blood flow in people with compromised endothelial function (hypertension, diabetes, aging). In young, healthy people with normal endothelial function, the acute circulatory effects of NO precursors are much smaller and often undetectable in studies [19].
“NO boosters give you better pumps in the gym”
Loosely supported, mostly cosmetic. The “pump” (exercise-induced hyperemia) is primarily driven by local metabolic factors during exercise. NO precursors may modestly enhance this effect. But the pump is not a reliable proxy for muscle growth — it’s a transient hemodynamic event, not a growth signal [20].
“Nitric oxide supplements boost testosterone”
Not supported. There’s no credible evidence that NO precursors increase testosterone levels. This claim appears in some product marketing but has no basis in published research.
“NO supplements improve heart health”
Context-dependent. NO plays a critical role in cardiovascular health, and impaired NO production is a feature of atherosclerosis and endothelial dysfunction. But taking a citrulline supplement is not a substitute for blood pressure medication, statins, or lifestyle changes. NO precursors may be a complementary tool, not a replacement for medical treatment.
Safety and Drug Interactions
NO precursor supplements are generally well-tolerated, but there are real considerations:
- Blood pressure medications: NO precursors can add to the blood pressure–lowering effects of antihypertensives. This isn’t necessarily dangerous but should be monitored, especially with nitrates and PDE5 inhibitors (sildenafil, tadalafil) — the combination can cause dangerous hypotension [21].
- Anticoagulants: Nitric oxide affects platelet aggregation. Theoretical interaction with blood thinners, though clinically significant problems are rare at supplement doses.
- GI effects: L-arginine at high doses (>10 g) commonly causes nausea, bloating, and diarrhea. L-citrulline is better tolerated. Beetroot juice can cause red urine/stool (beeturia), which is harmless but alarming.
- Kidney disease: Arginine metabolism is altered in kidney disease. Consult a doctor before supplementing.
How to Choose a Nitric Oxide Supplement
If your goal is blood pressure support: L-citrulline (3–6 g/day) or beetroot juice/concentrate (~6 mmol nitrate) have the most consistent evidence. They work through different pathways and may complement each other.
If your goal is exercise performance: Beetroot juice/nitrate (6–12 mmol, 2–3 hours pre-exercise) for endurance; citrulline malate (6–8 g pre-workout) for resistance training. Expect modest improvements, not miracles.
If your goal is erectile function: L-arginine (3–5 g/day) plus L-citrulline has some supporting evidence for mild ED. Talk to a doctor — this isn’t a substitute for proper evaluation.
What to avoid:
- Proprietary blends that hide doses behind “NO matrix” or “vasodilation complex” labels
- Products claiming 10x or 100x NO production — there’s no supplement that does this
- Capsule beetroot products that don’t declare nitrate content per serving
- Products relying solely on L-arginine when citrulline would be more effective
The Bottom Line
Nitric oxide precursor supplements have genuine science behind them — particularly L-citrulline for blood pressure and resistance training, and dietary nitrate/beetroot for endurance performance and blood pressure. L-arginine is the weakest of the three for most purposes.
The effects are real but modest. If you’re expecting a dramatic transformation from any NO supplement, you’ll be disappointed. If you’re looking for a marginal, evidence-backed edge on top of good training, nutrition, and (if relevant) medical management, then certain NO precursors are among the better-supported options in the supplement world.
References
[1] Förstermann, U., & Sessa, W.C. (2012). Nitric oxide synthases: regulation and function. European Heart Journal, 33(7), 829–837.
[2] Lundberg, J.O., Weitzberg, E., & Gladwin, M.T. (2008). The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics. Nature Reviews Drug Discovery, 7(2), 156–167.
[3] Woessner, M., et al. (2016). A stepwise reduction in plasma and salivary nitrite with increasing strengths of mouthwash following a dietary nitrate load. Nitric Oxide, 54, 1–7.
[4] Schwedhelm, E., et al. (2008). Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. British Journal of Clinical Pharmacology, 65(1), 51–59.
[5] Barkhidarian, B., et al. (2019). Effects of L-citrulline supplementation on blood pressure: a systematic review and meta-analysis. Avicenna Journal of Phytomedicine, 9(1), 10–20.
[6] Trexler, E.T., et al. (2019). Effects of citrulline supplementation on exercise performance: a review of the current literature. Journal of Sport and Health Science, 8(5), 401–410.
[7] Pérez-Guisado, J., & Jakeman, P.M. (2010). Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. Journal of Strength and Conditioning Research, 24(5), 1215–1222.
[8] Gonzalez, A.M., & Trexler, E.T. (2020). Effects of citrulline supplementation on exercise performance in humans: a review of the current literature. Journal of Strength and Conditioning Research, 34(5), 1480–1495.
[9] Bode-Böger, S.M., et al. (1998). L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. British Journal of Clinical Pharmacology, 46(5), 489–497.
[10] Bahadoran, Z., et al. (2021). Effects of L-arginine supplementation on blood pressure: a systematic review and meta-analysis. Nutrition, Metabolism and Cardiovascular Diseases, 31(5), 1424–1432.
[11] Rhim, H.C., et al. (2019). The potential role of arginine supplements on erectile dysfunction: a systematic review and meta-analysis. Journal of Sexual Medicine, 16(2), 223–234.
[12] Viribay, A., et al. (2020). Effects of arginine supplementation on athletic performance based on energy metabolism: a systematic review and meta-analysis. Nutrients, 12(5), 1300.
[13] Bailey, S.J., et al. (2009). Dietary nitrate supplementation reduces the O₂ cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. Journal of Applied Physiology, 107(4), 1144–1155.
[14] McMahon, N.F., Leveritt, M.D., & Pavey, T.G. (2017). The effect of dietary nitrate supplementation on endurance exercise performance in healthy adults: a systematic review and meta-analysis. Sports Medicine, 47(4), 735–756.
[15] Siervo, M., et al. (2013). Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis. Journal of Nutrition, 143(6), 818–826.
[16] Jackson, J.K., et al. (2018). The effect of inorganic nitrate supplementation on exercise performance: a systematic review and meta-analysis. Nutrients, 10(12), 1887.
[17] Wightman, E.L., et al. (2015). Dietary nitrate modulates cerebral blood flow parameters and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Physiology & Behavior, 149, 149–158.
[18] Jones, A.M., Thompson, C., Wylie, L.J., & Vanhatalo, A. (2018). Dietary nitrate and physical performance. Annual Review of Food Science and Technology, 9, 367–386.
[19] Chirinos, J.A., et al. (2005). Effect of oral L-arginine on functional capacity and vascular function in heart failure with preserved ejection fraction. Journal of the American College of Cardiology, 46(7), 1301–1308.
[20] Schoenfeld, B.J., & Contreras, B. (2014). The muscle pump: potential mechanisms and applications for enhancing hypertrophic adaptations. Strength and Conditioning Journal, 36(3), 21–25.
[21] Webb, D.J., et al. (1999). Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patients with stable angina. Journal of the American College of Cardiology, 33(1), 273–279.
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