Citrulline vs arginine: why we chose the one nobody has heard of

The lining of your blood vessels makes nitric oxide from an amino acid called L-arginine. That makes arginine the obvious thing to supplement, and for thirty years it has been. Open a "nitric oxide booster" and arginine is usually the first ingredient. It is also usually the reason the product doesn't do much.

The problem with swallowing arginine

Arginine that you swallow has to get past your gut and your liver before it reaches your blood. Both contain an enzyme, arginase, whose job is to break arginine down. Studies of oral arginine put its bioavailability somewhere between about 20 and 70 percent, and it falls as the dose rises:^{1 2} the more you take, the greater the share destroyed on the way in. Roughly 40 percent of dietary arginine is extracted by the gut alone.³ Then there is the gut itself. Arginine at the doses needed for a vascular effect, typically 9 grams a day and more, is associated with diarrhoea, nausea and cramps.⁴ So you take a lot, lose most of it, and feel the rest.

Citrulline takes the long way round

L-citrulline is a different amino acid, found in watermelon, and the body turns it into arginine. The difference is where. Citrulline is not a substrate for arginase, so it passes through the gut and liver largely untouched. It travels to the kidneys, which convert it to arginine and release that arginine into the blood.⁵ Taken orally, citrulline raises blood arginine more effectively than the same dose of arginine does.⁶

Citrulline skips the liver, converts in the kidneys and arrives intact. Arginine mostly doesn't arrive.

It is also well tolerated. In a dose-ranging study, up to 15 grams of citrulline in a single dose
produced no gastrointestinal side effects.⁷ And the blood pressure trials, at 3 to 9 grams a day, showed an average systolic reduction of about 4 mmHg and improved arterial stiffness.^{8 9}

Why the dose matters as much as the ingredient

Choosing citrulline is only half the decision. The trials used grams, not milligrams. A product with 250mg of citrulline is using the word, not the evidence. PowderMAX carries 3,000mg, the lower end of the trial range, in one scoop. HeartHealth-BP carries 2,000mg across six capsules; we say plainly that this is a supporting dose, because you cannot fit three grams of anything into six capsules alongside the rest of the formula.

What this means for you

If you have tried an arginine product and felt nothing, or felt it mostly in your stomach, the ingredient wasn't wrong. The route was. Your own nitric oxide pathway fades with age; feeding it with something that arrives is the first step in keeping it working.