Not all men with erectile dysfunction (ED) respond to treatment with phosphodiesterase type 5 (PDE5) inhibitors, but researchers have found that supplementing the treatment with a combination of oral L-citrulline and transresveratrol might help.
PDE5 inhibitors (such as sildenafil, vardenafil, and tadalafil) are considered a first-line treatment for ED. And while they are effective for many, the therapy doesn’t work for all patients. In addition, men who take nitrates are unable to take PDE5 inhibitors at all.
Vacuum erection devices, self-injections, and penile implants are effective alternatives, but they can be painful or inconvenient. As a result, fewer men choose these options.
In an effort to find more palatable ED treatment options, researchers have been investigating two substances: L-citrulline and resveratrol.
L-citrulline is an amino acid that converts to another amino acid called L-arginine, which creates nitric oxide and, in turn, can improve blood flow to the penis.
Transresveratrol is a polyphenol that can increase blood flow by improving endothelial function. (The endothelium is tissue that lines blood vessels, including those in the penis.)
Encouraging results from animal trials have led researchers to investigate the use of the two substances combined along with PDE5 inhibitors in men with ED.
The study began with 20 men between the ages of 29 and 78 (average age 61 years) in Japan. All of the men had moderate-to-severe ED. They were randomly assigned to one of two groups:
- Group A took a supplement capsule containing L-citrulline and transresveratrol along with an on-demand PDE5 inhibitor once a day for 30 days.
- Group B took a placebo (sugar pill) and an on-demand PDE5 inhibitor for 30 days.
After 30 days, both groups switched treatments for an additional 30 days. Study participants received questionnaires to assess erectile function (Sexual Health Inventory for Men [SHIM] and the Erection Hardness Score [EHS]), libido, and sexual performance.
Thirteen men completed the study. Men receiving the combined PDE5 inhibitor and L-citrulline / transresveratrol experienced slightly higher SHIM scores but no change in the EHS scores compared to those receiving PDE5 inhibitor and placebo.
“The present combination therapy might be more effective in improving confidence and satisfaction,” the authors remarked.
“There was little change in libido and sexual performance,” they added.
They acknowledged that their study duration was short, with a small group of participants. However, they plan further studies with more participants and longer durations.
Experts also caution that the study has many shortcomings, including too small of a sample size, high dropout rate, unclear baseline group matchings, and non-clinically significant changes in outcomes. They suggest that these results should not be interpreted to conclude that the addition of L-citrulline / transresveratrol results in any significant or meaningful increase in erectile function.
The study was published online in August in Sexual Medicine as an article in press.
“Are L-Citrulline Supplements a Safe Treatment for Erectile Dysfunction?”
(Reviewed: June 28, 2017)
Shirai, Masato, MD, PhD, et al.
“Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men With Phosphodiesterase 5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study”
(Full-text. Article in press. Published online: August 24, 2018)