Nitric Oxide Benefits: 8 Reasons It Matters

Written by Jeff Butterworth, ND. Reviewed March 2026.

Most people have never heard of nitric oxide. Yet this tiny signalling molecule is one of the most important regulators of human cardiovascular, metabolic, and cognitive health — and our ability to produce it drops by more than half between our 20s and our 50s.¹

This article covers what nitric oxide is, why its age-related decline matters, and the eight specific systems it supports — along with what the clinical evidence says about restoring it.

What is nitric oxide?

Nitric oxide (NO) is a gas produced in the cells lining your blood vessels — the endothelium — from the amino acids L-arginine and L-citrulline by an enzyme called endothelial nitric oxide synthase (eNOS).² Once released, it signals surrounding smooth muscle to relax, which widens blood vessels, improves blood flow, and lowers the pressure inside the vessel. It also has independent effects on inflammation, stem cell activity, platelet function, and mitochondrial energy production.

Louis Ignarro, Robert Furchgott, and Ferid Murad won the 1998 Nobel Prize in Physiology or Medicine for discovering that nitric oxide acts as a signalling molecule in the cardiovascular system. The research that followed has turned NO from a biological curiosity into one of the most studied targets in cardiology, sports science, and healthy-aging research.

Why nitric oxide matters more after 40

Endothelial function — the ability of blood vessels to produce NO and respond to it — declines steadily with age. Classic work by Taddei and colleagues showed a greater-than-50% loss of endothelium-dependent vasodilation in older adults compared with younger ones.¹ A 2015 review in the Journal of the American Heart Association summarised this as "aging of the nitric oxide system" — the cumulative effect of reduced eNOS activity, increased oxidative stress, and accelerated breakdown of NO.²

This decline is one reason the same lifestyle that felt easy at 25 starts producing fatigue, higher blood pressure, slower recovery, and mental fog at 45. Many of the symptoms associated with "getting older" trace back, at least in part, to the nitric oxide system working less well.

The 8 systems nitric oxide supports

1. Blood pressure and circulation

NO's best-known role is vasodilation — relaxing the smooth muscle in blood vessel walls so they widen. Higher NO availability lowers systolic and diastolic blood pressure, and improves oxygen delivery to every organ. Conversely, low NO availability is a core feature of hypertension.²

This is not just mechanistic theory. Clinical trials show that raising NO levels through dietary nitrate (beetroot juice) or L-citrulline supplementation produces measurable drops in blood pressure. A 2022 meta-analysis of beetroot juice trials in hypertensive patients found a 3.55 mmHg reduction in systolic and a 1.32 mmHg reduction in diastolic pressure.³ A systematic review of L-citrulline trials reported similar results — roughly a 4 mmHg systolic reduction, with stronger effects at doses of 6 g/day or more.⁴

2. Endothelial health and cardiovascular protection

The endothelium is the thin cell layer lining every blood vessel in the body. Healthy endothelial cells continuously produce NO to regulate flow, prevent platelet clumping, and suppress inflammation at the vessel wall. Endothelial dysfunction — the failure of this system — is now considered one of the earliest detectable stages of cardiovascular disease, preceding plaque, clinical hypertension, and events by years or decades.²

Supporting NO production is therefore not just about managing a symptom; it addresses a foundational driver of long-term vascular disease.

3. Cholesterol and plaque prevention

NO contributes to vascular protection beyond vasodilation. It helps limit the oxidation of LDL cholesterol (oxidised LDL is the form that drives plaque formation), reduces chronic vessel-wall inflammation, and inhibits the adhesion of white blood cells and platelets to the endothelium.² When NO availability falls, these protective effects fall with it, and the environment becomes more favourable to atherosclerosis.

4. Stem cell mobilisation and tissue repair

One of the more surprising findings about NO is its role in regeneration. Endothelial nitric oxide synthase is essential for mobilising stem and progenitor cells from the bone marrow — the cells the body uses to repair blood vessels and tissue after injury. A landmark 2003 study in Nature Medicine showed that eNOS-deficient mice fail to mobilise these progenitor cells properly and have impaired new-vessel formation.⁵ More recent work has extended this to vascular regeneration generally.

This is why low NO levels don't just affect how you feel today; they affect how well your cardiovascular system repairs itself over time.

5. Anti-inflammatory effects

At physiological levels produced by eNOS, NO has a suppressive effect on vascular inflammation. It reduces the expression of adhesion molecules that recruit immune cells to the vessel wall, and it damps the inflammatory signalling that contributes to both cardiovascular and metabolic disease.² (At much higher concentrations produced by inducible NOS during infection, NO acts differently — context matters.)

6. Exercise performance and recovery

Dietary nitrate and other NO-supporting strategies are among the most widely studied ergogenic aids in sports science. A 2024 review in Frontiers in Physiology summarised the mechanisms: NO increases blood flow to active muscle, improves mitochondrial efficiency, reduces the oxygen cost of exercise, and may stimulate mitochondrial biogenesis through AMPK and PGC-1α signalling.⁶

The practical effects are most pronounced in recreational exercisers and older adults — highly trained athletes see smaller benefits because their systems are already close to optimised.⁶

7. Energy and metabolic health

Because NO helps insulin signal properly and drives blood flow into skeletal muscle, it plays a meaningful role in glucose metabolism. Insulin itself triggers NO production in the endothelium, which then diverts blood flow to muscle tissue where glucose is taken up.⁷ When NO availability is low, this insulin-mediated flow response is blunted, contributing to insulin resistance.

Endothelial NO function and insulin sensitivity are positively correlated in healthy humans,⁷ which is one of the mechanistic links between metabolic syndrome and cardiovascular disease.

8. Cognitive function and brain health

The brain is extraordinarily blood-flow-sensitive. NO is the primary molecule coupling local neuronal activity to local blood flow — a process called neurovascular coupling. It also appears to support the long-term potentiation that underlies learning and memory.⁸

Reduced NO bioavailability is implicated in age-related cognitive decline and has been linked to the cerebral hypoperfusion seen in Alzheimer's disease.⁹ A 2022 review in the American Heart Association's journal Stroke argued that preserving endothelial NO function is emerging as a target for protecting cognitive health in aging.⁸

How to support nitric oxide naturally

Most practical NO-support strategies fall into two categories:

Increase the raw materials. Dietary nitrate (from beetroot, rocket/arugula, spinach, and other leafy greens) and the amino acid precursors L-arginine and L-citrulline provide the substrate the body uses to produce NO. Clinical trials consistently show blood pressure reductions with dietary nitrate and L-citrulline supplementation.^3,4
Protect the NO you already make. Oxidative stress breaks NO down before it can signal. Reducing inflammation and supporting antioxidant capacity — through diet, exercise, and targeted nutrition — preserves the NO that eNOS produces. Regular aerobic exercise is the single best-studied intervention for maintaining NO production with age.¹

The Butterworth Health approach: Ultimate 4 + BOOST

Two formulations address these two pathways.

Ultimate 4 is designed to directly support NO production, combining arugula extract (a concentrated source of dietary nitrate) with L-citrulline, the amino acid precursor that bypasses some of the first-pass metabolism that limits L-arginine supplementation.

BOOST addresses the inflammatory and metabolic environment that either protects or degrades NO once it's produced. It combines nutrient-dense plant compounds and medicinal mushrooms to support immune balance, reduce oxidative load, and improve metabolic function.

Used together, the two products address both sides of the equation — producing more NO and protecting the NO you produce from being broken down prematurely.

Key takeaways

Nitric oxide is a signalling molecule produced in your blood vessels that controls blood flow, protects the endothelium, and supports every system that depends on circulation.
NO production declines by more than 50% between the 20s and the 50s, and this decline contributes to many of the symptoms associated with aging.
Clinical trials show that dietary nitrate (beetroot) and L-citrulline supplementation produce measurable reductions in blood pressure.
Supporting NO is one of the few interventions with direct effects on cardiovascular, metabolic, exercise, and cognitive systems simultaneously.

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The Power of Nitric Oxide: 8 essential reasons why it should be your No. 1 supplement