Investigating arginine for erectile dysfunction

Introduction

Erectile dysfunction (ED) affects 18%^[1] of all men over the age of 20 in the United States, with roughly 45%^[1] of men over 20 and roughly 50% of all men aged 40-70 reporting at least some issues with erectile function. While increasing age is the biggest risk factor for ED, there are a host of other contributing factors^[1], such as diabetes, vascular disease, low testosterone^[2], and hypothyroidism^[3]. The main mechanism^[4] responsible for an erection is an increase in arterial blood flow to the penis through relaxation of the arterial and smooth muscle in the corpus cavernosum, which is spongy tissue running down the length of the penis. When the smooth muscle relaxes, blood flow increases into the corpus cavernosum, causing an erection. Disruption in this process is the primary cause of ED. Therapeutic agents for ED are aimed at restoring normal vascular function, specifically vasodilation^[5], the widening of blood vessels via relaxation of smooth muscle cells in the vasculature.

Nitric oxide (NO) is the molecule that is responsible for vasodilation in the penis and is the primary target of many pharmaceutical agents. NO^[6] works by causing cyclic guanosine monophosphate (cGMP) release inside cells, which signals for smooth muscle relaxation and vasodilation, allowing more blood to flow into the penis, thereby causing erections. Erections are sustained until cGMP is degraded by another molecule, phosphodiesterase (PDE) (Figure 1). PDE inhibitors^[7], like Viagra, are the main pharmaceutical agent used to treat ED. However, headaches, indigestion, abdominal pain, and flushing are common adverse effects^[7] of PDE inhibitors. Furthermore, these drugs don’t work^[8] in some people. These issues mean that there’s room for other possible ways to improve ED.

Possible alternatives to these pharmaceutical agents are nutraceutical options. One nutraceutical in particular, L-arginine, has been a focus of many studies. L-arginine provides NO to the body through a reaction that turns L-arginine into L-citrulline (Figure 1). There have been several randomized controlled trials that have examined the effect of L-arginine on ED with some trials^[9] showing a benefit, and other trials^[10] showing no benefit. The present study aimed to synthesize the evidence via meta-analysis in order to examine what the overall literature has to say about the effect of L-arginine on ED.

Erectile dysfunction affects roughly half of all men aged 40-70. Nitric oxide is one of the key regulators of vasodilation that controls blood flow to the penis, allowing for erections to occur. L-arginine is one of the substrates in the human body that can be converted into nitric oxide. The present study was a meta-analysis that examined the effect of L-arginine supplementation on ED.