Guide · vessel biology
Nitric oxide and blood vessels: how arginine fits in
Nitric oxide is a signaling molecule that tells the muscle in blood vessel walls to relax. Enzymes called nitric oxide synthases make it from the amino acid L-arginine, releasing L-citrulline as they go. That is the pathway Melonex points to with its arginine and citrulline blend, though no study has measured nitric oxide after taking the capsules.
Written by the Melonex label deskUpdated
The molecule01
What is nitric oxide in the body?
Nitric oxide, often written NO, is a small signaling molecule the body makes on demand. In blood vessels its main job is to tell the muscle layer in the wall to relax (Cziraki 2020, arginine-NO pathway).
Three enzymes make it. They are called nitric oxide synthases: an endothelial form in the vessel lining, a neuronal form in nerve tissue and an inducible form (Cziraki 2020, arginine-NO pathway).
All three start from the same raw material, the amino acid L-arginine. Each time they make nitric oxide, they also release L-citrulline (Cziraki 2020, arginine-NO pathway).
The mechanism02
How does nitric oxide relax blood vessels?
Nitric oxide relaxes blood vessels by raising a messenger called cyclic GMP inside the smooth muscle cells of the vessel wall. Higher cyclic GMP carries most of nitric oxide's effect in large vessels, including widening (Cziraki 2020, arginine-NO pathway).
The chain starts in the thin lining of the vessel. The lining makes nitric oxide, it passes to the muscle layer, and the muscle eases. A wider vessel lets blood through with less push.
- 01
Arginine arrives
From food, from the body's own supply or from citrulline.
- 02
Synthase works
The enzyme turns arginine into nitric oxide plus citrulline.
- 03
Cyclic GMP rises
Nitric oxide raises the messenger in the muscle cells.
- 04
The wall relaxes
The muscle layer eases and the vessel widens.
A simplified outline of the pathway described in a 2020 review (Cziraki 2020, arginine-NO pathway). Real vessels respond to many signals at once.
The raw material03
Where do arginine and citrulline fit in making nitric oxide?
Arginine is the direct raw material, and citrulline is both a by-product and a back door. The synthase enzymes use arginine and give off citrulline (Cziraki 2020, arginine-NO pathway).
The kidneys can turn citrulline into arginine again. About 83% of what they take up is converted, so swallowed citrulline ends up raising blood arginine (Aguayo 2021, L-citrulline review).
In one dosing study, oral citrulline lifted blood arginine more than oral arginine did and boosted nitric oxide signaling in a dose-dependent way (Schwedhelm 2008, citrulline kinetics). The full comparison is in arginine vs citrulline.
A puzzle04
What is the arginine paradox?
The arginine paradox is the finding that extra arginine can improve vessel widening even though the endothelial enzyme normally has plenty of arginine already (Cziraki 2020, arginine-NO pathway). On paper, more raw material should not help a factory that is not short of it.
One part of the answer involves a natural blocker called ADMA. It slows the synthase enzyme and cuts nitric oxide release (Cziraki 2020, arginine-NO pathway).
An enzyme called DDAH breaks ADMA down into citrulline and dimethylamine (Cziraki 2020, arginine-NO pathway). So the balance between arginine and ADMA, not arginine alone, shapes how much nitric oxide a vessel makes.
Arginine
The raw material that nitric oxide synthase turns into nitric oxide.
ADMA
A natural blocker that slows the enzyme and lowers nitric oxide release.
DDAH
The enzyme that clears ADMA, leaving citrulline behind.
Melonex: from $49 a bottle60 capsules · 2, 3 or 6 bottles · free US shipping on 3 or 6 · 60-day guarantee
See packsWords that sound alike05
Are nitrates, nitric oxide boosters and nitrate drugs the same thing?
No. Three different things share the nitric oxide story, and mixing them up can be dangerous. Dietary nitrate comes from foods like beetroot, nitrate drugs are prescription heart medicines, and amino acid supplements supply arginine or citrulline.
Beetroot juice and inorganic nitrate lowered systolic pressure by about 4.4 mm Hg across 16 short trials (Siervo 2013, nitrate meta-analysis). Nitrate drugs such as nitroglycerin are prescribed for chest pain (MedlinePlus, sildenafil).
| Type | Examples | What research shows | Main caution |
|---|---|---|---|
| Amino acid supplements | L-arginine, L-citrulline (Melonex) | Small blood pressure drops at 3-24 g a day (Dong 2011, arginine meta-analysis) (Barkhidarian 2019, citrulline meta-analysis) | May add to heart and blood pressure drugs (Mayo Clinic, L-arginine) |
| Dietary nitrate | Beetroot juice, inorganic nitrate | About 4.4 mm Hg lower systolic in 16 trials lasting up to 15 days (Siervo 2013, nitrate meta-analysis) | Longer trials still needed |
| Nitrate medicines | Nitroglycerin, isosorbide dinitrate or mononitrate | Prescription drugs for chest pain | Never with sildenafil (MedlinePlus, sildenafil) |
Safety06
Why can nitric oxide supplements be risky with heart drugs?
They can stack on top of drugs that already widen vessels. Mayo Clinic warns that arginine with blood pressure drugs, nitrates or sildenafil might drop blood pressure too low (Mayo Clinic, L-arginine).
Sildenafil and nitrate medicines must never be taken together (MedlinePlus, sildenafil). FDA has also found hidden sildenafil in products sold as sexual-enhancement supplements, a real risk for anyone on nitrates (FDA, hidden drug notice).
Low blood pressure means a reading below 90/60. Dizziness, fainting, blurry vision or confusion are signs to sit down and call your doctor (NHLBI, low blood pressure).
Never trade a nitrate or a blood pressure drug for a supplement that works on the same pathway. Tell your doctor about every capsule you take. More on supplements and heart medicines.
In Melonex07
Can a Melonex capsule raise nitric oxide?
Nobody knows, because no study has measured nitric oxide after anyone took Melonex. The capsules hold the right raw materials, arginine and citrulline, but in small amounts.
The study that saw citrulline boost nitric oxide signaling used up to 3 g twice a day (Schwedhelm 2008, citrulline kinetics). Two Melonex capsules hold 1 g of blend in all, split three ways and including salt partners.
The "Circulation Support*" icon on the label rests on this pathway. It is a structure/function claim with the FDA asterisk, not proof of an effect (FDA, structure/function claims). The step-by-step version is on how Melonex works, and the amounts on the Melonex dose check.
- Right pathway: arginine and citrulline both feed nitric oxide
- Small dose: 0.5-1 g of blend a day, against 3 g or more in studies
- No measurement: nitric oxide was never tested with the product
FAQ08
Nitric oxide questions
Which enzymes make nitric oxide?
Three nitric oxide synthases make it: an endothelial form in the vessel lining, a neuronal form and an inducible form. All three use L-arginine as the raw material and give off L-citrulline along with nitric oxide (Cziraki 2020, arginine-NO pathway).
What is cyclic GMP?
Cyclic GMP is a messenger inside smooth muscle cells. Nitric oxide raises it in the vessel wall, and that rise carries most of nitric oxide's effect in large vessels, including the widening that lets blood flow more easily (Cziraki 2020, arginine-NO pathway).
What is ADMA and why does it matter?
ADMA, short for asymmetric dimethylarginine, is a natural compound that slows nitric oxide synthase and lowers nitric oxide release. The enzyme DDAH breaks it down into citrulline and dimethylamine (Cziraki 2020, arginine-NO pathway).
Does citrulline make nitric oxide directly?
No, citrulline works through arginine. The kidneys turn most of it into arginine, and arginine is what the synthase enzymes use (Aguayo 2021, L-citrulline review) (Cziraki 2020, arginine-NO pathway). Citrulline is also a by-product each time nitric oxide is made.
Is beetroot juice a nitric oxide supplement?
Beetroot juice supplies dietary nitrate, a different starting point from arginine or citrulline. In 16 short trials, inorganic nitrate and beetroot juice lowered systolic pressure by about 4.4 mm Hg (Siervo 2013, nitrate meta-analysis). Melonex contains no beetroot or nitrate.
Does FDA approve nitric oxide booster supplements?
No. FDA does not approve any dietary supplement or its label before it is sold (FDA, supplement Q&A). Makers are responsible for safety and truthful claims, and FDA acts mainly after a product reaches the market.
Why must sildenafil never be taken with nitroglycerin?
Both widen blood vessels, and together they can drop blood pressure to dangerous levels. MedlinePlus says sildenafil should not be taken with nitrate chest-pain drugs such as nitroglycerin or isosorbide (MedlinePlus, sildenafil).
Who wrote this09
Written and reviewed by
Pages built from the label, the sales page and linked NIH, FDA, AHA, CDC, FTC and peer-reviewed sources.
Last updated . Read our editorial standards and how we check reviews. This website is run by a USA authorized Melonex retailer, not by the manufacturer or the distributor. We earn money when you buy through our order links.
Keep reading
More about Melonex
USA authorized Melonex retailer
Ready to try Melonex?
Check your medicines first, then pick a pack. Three or six bottles ship free in the US and cost less per bottle, and the 60-day guarantee opens after 30 days of use.
- Secure checkout
- 60-day guarantee
- Ships from the U.S.
