Citrulline is an amino acid marketed as a supplement with the promise of guaranteeing more vigorous and lasting erections. Not surprisingly, the generous presence of citrulline is called into question to justify the alleged aphrodisiac properties of the watermelon from a scientific point of view.
Citrulline, nitric oxide and penile erection
The rationale for the use of 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 guanylate cyclase enzyme, nitric oxide produces a vasodilation increasing the turgor of the corpora cavernosa and contributing in a decisive way to the erection of the penis
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 Piroglutamate, Arginine Ethylester, Arginine Alfachetoglutarate). Some studies supporting the use of citrulline in the treatment of erectile dysfunction argue that oral administration of arginine would be hampered by 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. In addition, hepatic arginases expose the share 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. Unlike 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 in a dose-dependent manner both the plasma levels of arginine and those of citrulline. At the same dosage and route of administration (by mouth), citrulline would ensure an increase in blood arginine levels almost double those of the same dose of arginine at a slow dosage, and about 20% higher than those of the same immediate release arginine dose [1].
Is there evidence to support citrulline in the treatment of erectile dysfunction?
The effectiveness of citrulline in the treatment of erectile dysfunction has been tested in some preliminary clinical studies and on animal models, with incorrupting but certainly not miraculous results.
In a recent clinical study [2], 24 patients aged 56.5 years ± 9.8 years with erectile dysfunction LIEVE took a placebo for one month, and a daily dose of 1.5 g of L-citrulline during the following month.
The entire group completed the study without adverse events. In the month of placebo treatment there was an improvement in the hardness score of erection from 3 (mild erectile dysfunction) to 4 (normal erectile function) in only two patients (8.3% of the sample). During treatment with L-citrulline, on the other hand, the positive data was recorded in 12 subjects (50% of the sample).
The average number of monthly reports increased from the baseline value of 1.37 ± 0.93 to 1.53 ± 1.00 at the end of placebo treatment (P = .57) and at 2.3 ± 1.37 at the end of citrulline treatment.
All patients reporting an improvement in erection hardness scores 3 to 4 were very satisfied with the treatment received.
Based on the results of the study, according to the authors, although less effective than the classic inhibitors of the enzyme phosphodiesterase type 5 (tadalafil, vardenafil, sildenafil, avanafil ...), at least in the short term, citrulline is safe and psychologically well accepted. Its role as an alternative treatment of LIEVE 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 (1): 119-22.
Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction.
Cormio L, De Siati M, Lorusso F, Wild O, Mirabella L, Sanguedolce F, Carrieri G.
