L-Citrulline for Erectile Dysfunction

Promising but thin. L-citrulline is an amino acid the body turns into L-arginine and then nitric oxide, the signal behind penile erection [1]. In the only trial of citrulline on its own, 24 men with mild erectile dysfunction took a placebo for a month and then 1.5 g of L-citrulline a day for a month. Erection hardness reached normal in 12 of the 24 (50%) on citrulline and in 2 (8.3%) on placebo [1].

That trial was small, only the men were blinded, and everyone took placebo first, so it cannot rule out a learning or expectation effect. Every other trial gave citrulline in a mix with resveratrol, pine bark, arginine or other ingredients [2][3]. A 2024 network meta-analysis of 15 placebo-controlled trials found that, among supplements, only L-arginine (alone or with tadalafil) and a carnitine mix taken with sildenafil beat placebo; its abstract reports no citrulline-only arm [4]. So the verdict is insufficient evidence, with an early positive signal.

Penile erection runs on the L-arginine to nitric oxide pathway. Much of an oral arginine dose is broken down before it reaches the blood [1]; the gut enzyme arginase is the main reason [5].

Citrulline avoids that. In a randomised crossover study in 20 healthy volunteers, oral L-citrulline raised blood arginine more effectively than arginine did, and 3 g twice a day raised urinary nitrate and cGMP, markers of nitric oxide signalling [5]. This is why citrulline is often described as a better way to supply arginine than arginine itself (see L-arginine for ED).

Raising nitric oxide markers is not the same as improving erections. In the same volunteer study, no regimen improved flow-mediated dilation (a measure of blood vessel function) over baseline, although pooled data linked larger rises in the arginine/ADMA ratio to better dilation [5]. PDE5 inhibitors such as sildenafil remain the first-line drug treatment for most men with ED [2].

In 122 men with ED, blood arginine and citrulline were lower in those whose ED had an arterial cause than in controls, but levels across all ED patients were not different from controls [6]. That suggests a possible link in some men, not that a supplement corrects ED.

The only citrulline-alone ED trial used 1.5 g of L-citrulline a day for one month [1]. The abstract does not say whether the dose was split or taken with food. Combination trials used 800 mg a day with trans-resveratrol for one month, or in a drink with three other ingredients for two weeks [2][7].

Citrulline is also sold as citrulline malate, so check the label states how much L-citrulline a dose provides. In healthy men, single doses up to 15 g caused no side effects, but at the highest doses arginine rose less than expected, so more is not obviously better [8].

Cormio and colleagues gave 24 men with mild ED (mean age 56.5) a placebo for one month and then 1.5 g of L-citrulline a day for one month. The men did not know which they were taking, but the order was the same for everyone. Normal erection hardness was reached by 2 men (8.3%) on placebo and 12 (50%) on citrulline (P < .01). Intercourse rose from 1.37 a month at baseline to 1.53 on placebo (not significant) and 2.3 on citrulline (P < .01). Every man whose score improved said he was very satisfied, and nobody reported side effects [1].

The authors called citrulline less effective than PDE5 inhibitors, at least in the short term, and said its role deserves further research [1]. No randomised, double-blind trial of citrulline alone has followed.

In a crossover pilot in men whose ED persisted on PDE5 inhibitors, a month of 800 mg citrulline plus 300 mg trans-resveratrol raised the SHIM questionnaire score to 10.96, against 8.31 on placebo (P < .05). Erection hardness did not change significantly, and only 13 of 20 men completed [2]. In 50 men with moderate ED, a month of pine bark extract, roburins, arginine and citrulline was reported to restore erectile function to normal, but the abstract gives no numbers [3].

A two-week pilot drink with fenugreek extract, citrulline, resveratrol and caffeine improved several IIEF items in 20 men already using PDE5 inhibitors [7]. In a 3-month trial without a placebo group, a nine-ingredient sachet containing citrulline added 7.4 IIEF-5 points with tadalafil, against 5.1 for tadalafil alone [9]. None of these designs can show what the citrulline itself did.

A 2024 network meta-analysis of 15 placebo-controlled trials in 1,000 men ranked supplements and drugs for ED. Compared with placebo, only a carnitine mix with sildenafil, L-arginine with tadalafil, sildenafil, tadalafil and L-arginine alone worked; no other regimen reached significance [4]. A 2023 meta-analysis identified some ingredients, such as ginseng, tribulus and L-arginine, that can improve male sexual function, and judged 20 of 25 ED supplements sold in Italy (80%) to have no expected efficacy [10].

For comparison, a meta-analysis of 10 randomised trials found L-arginine at 1,500 to 5,000 mg a day improved mild to moderate ED [11]. The American Urological Association guideline asks clinicians to inform men of every suitable treatment and decide together, weighing the benefits and burdens of each. It also says men should be told that ED is a risk marker for underlying heart disease and other conditions, such as undiagnosed diabetes, that may need checking and treatment [12].

There is no randomised, double-blind, placebo-controlled trial of citrulline alone in ED, no trial longer than a month for citrulline alone, and no trial in moderate or severe ED. In men after prostate surgery, a clinic that started tadalafil and citrulline before the operation saw more men regain erections by 12 months (56% vs 24%), but that review compared timing, not citrulline against no citrulline [13].

No adverse events were reported in the citrulline-alone ED trial at 1.5 g a day [1], in the two citrulline combination pilots [2][7], or in healthy men given single doses up to 15 g [8]. The Natural Medicines monograph rates L-citrulline as possibly safe when used appropriately [14].

The main concern is blood pressure. The monograph says citrulline might lower blood pressure [14], although a meta-analysis of five trials found no significant effect on blood pressure [15]. There is not enough information on safety in pregnancy or breastfeeding, so the monograph advises avoiding it then [14].

Citrulline's interactions come from its effect on nitric oxide and blood vessels. The Natural Medicines monograph rates nitrates and PDE5 inhibitors as major interactions ("do not take this combination") and blood pressure medicines as moderate [14]. A professional interaction database is less strict: it rates arginine with sildenafil as moderate and advises closely monitoring blood pressure and heart rate when citrulline or arginine is used with nitrates or vasodilators [16]. Small trials that added citrulline products to PDE5 inhibitors reported no adverse events [2][7], but they were too small to rule out a risk.