Citrulline and Erectile Dysfunction

Citrulline is an amino acid marketed in supplement form with the promise of providing more vigorous and lasting erections. Not surprisingly, the generous presence of citrulline is called into question to justify the alleged aphrodisiac properties of watermelon from a scientific point of view.

Citrulline, Nitric Oxide and Penile Erection

The rationale for using the amino acid L-citrulline in the treatment of erectile dysfunction derives from its metabolic conversion into arginine, a semi-essential amino acid involved in the synthesis of nitric oxide (NO). At the penile level, through the stimulation of the enzyme guanylate cyclase, nitric oxide produces a vasodilation, increasing the turgor of the corpora cavernosa and contributing decisively to the erection of the penis

The biosynthesis of nitric oxide in endothelial cells and in other parts of the organism occurs mainly through the transformation of L-arginine into L-citrulline, operated by enzymes called NO synthase (NOS). As shown in the figure, the newly formed citrulline can in turn give rise to new arginine and the cycle begins again.

Starting from this metabolic assumption, the first amino acid supplements proposed for the treatment of erectile dysfunction mainly contained the "semi-essential amino acid L-arginine and its salts (eg. Arginine Pyroglutamate, Arginine Ethylester, Arginine Alfachetoglutarate). Some studies supporting the" use of citrulline in the treatment of erectile dysfunction claim that the oral administration of arginine would be hindered by the "extensive presystemic metabolism [1]. In particular, the generous presence of arginase in the intestine would lead to the conversion of a part of the arginine taken into ornithine and urea, inactivating the amino acid before it is absorbed. Hepatic arginases also expose the amount of arginine absorbed to an important first pass effect which further reduces the amount available at the systemic level for the synthesis of nitric oxide. "arginine," the amino acid L-citrulline is not subject to these forms of systemic and pre-systemic elimination, to the point that its administration increases both the plasma levels of arginine and those of citrulline in a dose-dependent manner. At the same dosage and route of administration (by mouth), citrulline would guarantee an increase in arginine levels in the blood almost double those of the same dose of slow-dosed arginine, and about 20% higher than those of the same immediate-release arginine dose [1].

Is there any evidence to support citrulline in the treatment of erectile dysfunction?

The efficacy of citrulline in the treatment of erectile dysfunction has been tested in some preliminary clinical studies and on animal models, with encouraging but certainly not miraculous results.

In a recent clinical study [2], 24 patients with a mean age of 56.5 years ± 9.8 years with Mild erectile dysfunction received a placebo for one month, and a daily dose of 1.5 g of L-citrulline during the following month.

The entire group concluded the study without adverse events. In the month of placebo treatment there was an improvement in the erection hardness score from 3 (mild erectile dysfunction) to 4 (normal erectile function) in only two patients (8.3 % of the sample). During the treatment with L-citrulline, however, the positive result was recorded in 12 subjects (50% of the sample).

The mean number of monthly reports increased from baseline of 1.37 ± 0.93 to 1.53 ± 1.00 at the end of placebo treatment (P = .57) and to 2.3 ± 1.37 at the end of citrulline treatment.

All patients who reported an improvement in the erection hardness score from 3 to 4 were very satisfied with the treatment received.

According to the results of the study, according to the authors, although less effective than the classic inhibitors of the phosphodiesterase type 5 enzyme (tadalafil, vardenafil, sildenafil, avanafil ...), at least in the short term, citrulline is safe and psychologically well Its role as an alternative treatment for mild erectile dysfunction, particularly in patients who struggle to psychologically accept PDE-5 inhibitor therapy, therefore deserves further research.

BIBLIOGRAPHY

[1] Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Germany.

Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism.
Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F, Böger RH.

[2] Urology. 2011 Jan; 77: 119-22.

Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction.

Cormio L, De Siati M, Lorusso F, Selvaggio O, Mirabella L, Sanguedolce F, Carrieri G.