What Supplement Increases Nitric Oxide the Most? A Deep Dive into Effectiveness

November 3, 2025 •

4 min read

Multiple clinical reviews show that specific nitric oxide (NO) precursors can significantly improve exercise performance and heart health, especially in moderately trained individuals. Determining which supplement increases nitric oxide the most hinges on understanding the unique bioavailability and pathways of the most common options.

Quick Summary

This guide evaluates the supplements proven to raise nitric oxide levels, including L-citrulline, beetroot extract (nitrates), and Nitrosigine. It analyzes their mechanisms and effectiveness to pinpoint the most potent options for boosting circulation and performance.

Key Points

L-Citrulline is Highly Bioavailable: Unlike L-arginine, L-citrulline is efficiently converted to L-arginine in the kidneys, leading to higher and more sustained nitric oxide levels.
Beetroot Extract Follows a Unique Pathway: Dietary nitrates in beetroot are converted to nitric oxide via oral bacteria, a process that is particularly effective during exercise.
Nitrosigine Offers Potent, Fast-Acting Effects: This bonded arginine silicate complex increases blood vessel dilation and can be more potent by weight than L-citrulline.
Combine Supplements for Synergistic Effects: For both immediate and long-term benefits, a combination of L-citrulline and dietary nitrates or Nitrosigine can be highly effective.
Bioavailability is Key: The most effective supplements are those that deliver their precursors to the body's nitric oxide synthesis pathways most efficiently, making L-citrulline and Nitrosigine superior to standard L-arginine.
Don't Forget Natural Sources: Alongside supplements, a diet rich in nitrate-heavy vegetables, antioxidants, and regular exercise can naturally boost nitric oxide production.

Nitric oxide (NO) is a crucial signaling molecule in the body that plays a pivotal role in vasodilation, the process of relaxing and widening blood vessels. This improved blood flow allows for more efficient delivery of oxygen and nutrients to muscles and organs, which is why NO-boosting supplements are popular among athletes and individuals focused on cardiovascular wellness.

The Contenders: L-Citrulline, Beetroot, and Nitrosigine

While many supplements claim to boost NO, research consistently points to a few key ingredients as the most effective. These supplements don’t contain NO directly but provide precursors that the body converts into the gas.

L-Citrulline: The Bioavailable Amino Acid

L-citrulline is an amino acid that has gained prominence over its counterpart, L-arginine. The key reason for its superior effectiveness lies in its bioavailability. When you take L-citrulline orally, it bypasses metabolism in the liver and small intestine, traveling to the kidneys where it is efficiently converted into L-arginine. This process leads to higher and more sustained plasma L-arginine levels than supplementing with L-arginine directly, resulting in greater NO production.

Mechanism: L-citrulline -> L-arginine -> Nitric Oxide (via NOS enzyme)
Advantages: Superior absorption, sustained NO levels, and potential for reduced fatigue and improved aerobic performance.
Typical Dose: Research suggests a daily intake of 3–8 grams for optimal effects.

Beetroot Extract (Dietary Nitrates)

Beetroot extract is a powerhouse of dietary nitrates, which follow an entirely different, enzyme-independent pathway to produce NO.

Mechanism: Ingested nitrate -> Reduced to nitrite by oral bacteria -> Converted to NO in acidic stomach environments and tissues.
Key Insight: This pathway is particularly active when oxygen levels are low, such as during intense exercise, suggesting it can be a highly effective ergogenic aid.
Proven Effects: Studies have shown that beetroot juice supplementation can decrease the oxygen cost of exercise and enhance endurance performance.
Dosage: Effective doses typically correspond to around 300–550 mg of nitrate.

Nitrosigine (Inositol-Stabilized Arginine Silicate)

Nitrosigine is a patented, bonded form of arginine and silicate. It was developed to overcome the poor bioavailability of standard L-arginine. Studies have shown that Nitrosigine is highly effective at increasing vasodilation, often at a lower dose than L-citrulline, and its effects can be both fast-acting and long-lasting.

Mechanism: Increases serum arginine and silicon levels more effectively than standard arginine.
Comparison to L-citrulline: A 2020 study found that 1.5g of Nitrosigine and 8g of Citrulline Malate yielded a similar improvement in vasodilation, suggesting a higher potency by weight for Nitrosigine.
Advantages: Potent, requires a smaller dose for a comparable effect, and can act quickly.

Other Supportive Ingredients

Beyond these main players, other compounds can enhance NO production by protecting it from degradation or influencing related pathways. Antioxidants like Vitamin C, Vitamin E, and polyphenols found in sources like grape seed and pomegranate extract can help stabilize the volatile NO molecule, extending its effects.

Comparison of Top Nitric Oxide Supplements


Feature	L-Citrulline	Beetroot Extract (Nitrates)	Nitrosigine (Bonded Arginine)
Mechanism of Action	Converted to L-arginine in the kidneys to boost NOS pathway.	Reduced to nitrite by oral bacteria, then to NO in the body.	Increases serum arginine more effectively than standard L-arginine.
Bioavailability	High; bypasses liver metabolism for excellent absorption.	Variable depending on source, but consistently effective in studies.	Superior to L-arginine; specifically engineered for better absorption.
Onset of Effect	Takes time to convert, with effects building up over several days of use.	Acute effects seen within a few hours of consumption.	Fast-acting, increasing arginine levels in as little as 15 minutes.
Duration of Effect	Provides sustained, long-lasting elevation of arginine and NO.	Can have a potent, temporary effect, particularly pre-exercise.	Long-lasting, with benefits extending up to 6 hours from a single dose.
Typical Dose	3-8 grams per day.	300-550 mg of nitrate.	1.5 grams per day.
Best For	Sustained NO support for endurance and overall cardiovascular health.	Acute, pre-exercise boost for immediate performance improvement.	Rapid, powerful pre-workout pump and cognitive support.

Natural Ways to Boost Nitric Oxide

Supplements are not the only way to increase NO levels. Incorporating natural, food-based sources can also be highly effective and sustainable:

Nitrate-Rich Vegetables: Leafy greens like spinach and arugula, as well as celery and carrots, are excellent sources of nitrates.
Antioxidant-Rich Foods: Berries, dark chocolate, and citrus fruits are packed with antioxidants that help preserve NO.
Watermelon: This fruit is a natural source of L-citrulline.
Regular Exercise: Physical activity naturally stimulates the endothelium, the lining of blood vessels, to produce more NO.

The Power of Combination

For some, a blend of different supplements can offer a synergistic effect, combining the benefits of multiple pathways. For instance, combining L-citrulline for sustained NO production with a fast-acting nitrate source like beetroot can provide both immediate and long-lasting benefits. Research supports that combining L-citrulline and L-arginine can lead to higher plasma levels of arginine than either supplement alone.

Conclusion: So, What Increases Nitric Oxide the Most?

To definitively state one supplement increases nitric oxide the most is challenging, as effectiveness is influenced by bioavailability, dosage, and individual physiology. However, based on the body of evidence, L-citrulline is consistently highlighted for its superior bioavailability compared to L-arginine, leading to sustained NO production. For immediate, powerful vasodilation, Nitrosigine is highly effective at a lower dose. For those seeking a whole-food approach, beetroot extract provides a reliable nitrate source with proven ergogenic effects. For comprehensive and sustained results, a combination of L-citrulline, dietary nitrates, and protective antioxidants may be the most potent strategy. Always consult a healthcare professional before starting a new supplement regimen.

For further reading on the synthesis and benefits of nitric oxide, review this scientific article from the National Institutes of Health: Dietary supplements for improving nitric-oxide synthesis

Frequently Asked Questions

While L-citrulline and beetroot both show rapid effects, Nitrosigine is noted for increasing serum arginine levels in as little as 15 minutes, making it one of the fastest-acting options.

L-citrulline is generally considered more effective than L-arginine because it bypasses liver metabolism, leading to significantly higher and longer-lasting plasma L-arginine levels when converted in the kidneys.

Concentrated beetroot juice or extract powder is considered the most reliable form for consistent nitrate delivery, as the nitrate content in whole beets can vary. These forms are often standardized to ensure a specific nitrate dose.

Yes, combining supplements that use different pathways, such as L-citrulline (amino acid pathway) and beetroot (nitrate pathway), can offer synergistic effects for both immediate and sustained NO production.

Side effects for most NO supplements are mild and can include digestive upset, especially with high doses of L-arginine. Individuals with certain health conditions, like low blood pressure or herpes, should consult a doctor before use.

Naturally boost your NO levels by consuming nitrate-rich vegetables like spinach and beetroot, eating antioxidant-heavy foods, exercising regularly, and getting some sunlight exposure.

Studies generally show optimal effects with a daily dose ranging from 3 to 8 grams of L-citrulline, which can be split into smaller, spaced increments throughout the day.

Antioxidants help stabilize the unstable NO molecule, preventing it from breaking down too quickly in the bloodstream. This preservation makes the NO more available to the body for longer periods.