Arginine for a better erection?

Geschatte leestijd: 11 minuten

Arginine can strengthen an erection by increasing NO, thereby dilating the vessels of smooth muscle tissue in the corpora cavernosa of the penis.

How does an erection work?

While the initial sections on arginine mostly discussed its benefits related to athletic performance such as muscle mass and strength, endurance, and fat burning, this part is dedicated to another advantage attributed to arginine: its function as an enhancer of an erection.

In “What is arginine?” I described among other things that arginine can lead to increased production of nitric oxide, or NO. Besides, I mentioned that NO acts as a “neurotransmitter in the autonomic nervous system” and that in this capacity, it relaxes smooth muscle tissue including in the penis by dilating blood vessels. This dilation of the vessels allows more blood to be delivered to the penis, resulting in a (harder) erection.

The active ingredients in well-known erection drugs such as sildenafil (Viagra) and tadalafil (Cialis) work, albeit via a different pathway, in a similar way by relaxing the corpora cavernosa of the penis.

“The erection of Leonardo da Vinci”

Leonardo da Vinci, known among other things for dissecting cadavers to study anatomy, was the first to discover that the supply of blood is responsible for an erection (1).

The penis does not obey the order of its master, who tries to erect or shrink it at will, whereas instead the penis erects freely while its master is asleep. The penis must be said to have its own mind, by any stretch of the imagination.

-Leonardo da Vinci

“Action mode and rest mode”

Although it is a well-known claim that men think with their genitalia, and Da Vinci actually attributed “its own will” to this organ, subsequent research has shown that the central and autonomic nervous systems control the penis. Sexual stimulation causes signals to be emitted from the brain. These signals lead to the release of acetylcholine by the ends of parasympathetic nerves (part of the nervous system that controls functions in a state of “rest” such as eating, urinating, but also sexual arousal). The acetylcholine then leads to the release of NO. This happens both directly and via the endothelial cells in the penis (cells that cover the inside of blood vessels and the heart among others) (2).

At the same time, the function of the (ortho)sympathetic nervous system, the part that goes over the “action mode” of the body, is deactivated. When in “action mode,” when the (ortho)sympathetic nervous system is active, think of moments of stress, fear, anger, but also cold. That this “action mode” is not conducive to an erection can be deduced from the fact that many men think about sports, for example, to prevent an erection at an undesirable moment, to make it subside, or to prevent (premature) ejaculation. In practice, this prevents the penis from unnecessarily demanding a lot of blood and thus oxygen that you could use for “action,” whatever that action might be. Moreover, you can imagine that it would physically not be convenient to walk around with an erection during moments of physical activity (other than sex), apart from social consequences.

In the rest mode, when the parasympathetic nervous system is mainly active, the chance of an erection is enhanced. For example, during REM sleep, the orthosympathetic nervous system is deactivated, allowing a nocturnal erection to occur. Some researchers see this as a kind of “maintenance function for the penis” by periodically providing a flow of oxygen-rich blood at night (1).

Arousal

The release of NO does not directly cause relaxation of the blood vessels (imagine if it were that simple). The released NO gas acts as a signaling molecule and activates the enzyme guanylate cyclase (GC). GC then converts guanosine triphosphate (GTP) into cyclic guanosine monophosphate (cGMP). Eventually, it is the cGMP that causes the corpora cavernosa of the penis to relax. There are three corpora cavernosa, two on either side (corpora cavernosa penis) and one at the bottom (corpus spongiosum penis). Mainly the corpora cavernosa fill with blood, causing them to be pumped up, come under pressure, and nearly touch each other. This compression ensures that the blood, so to speak, remains trapped in the corpora cavernosa. This pressure is also important for ejaculation, which can only take place when the pressure is greater than the systolic blood pressure (“upper pressure”) (3).

Erection–>PDE5–>cGMP–>GMP

Conversely, an erection decreases through the action of enzymes called phosphodiesterase type 5 (PDE5). I have previously discussed PDE5 in the article about Horny Goat Weed. Horny Goat Weed, but also the much more effective components of Viagra and Cialis, act as so-called PDE5 inhibitors. Zey limit the action of this enzyme, which otherwise has a degrading effect on cGMP, converting it into the inactive GMP.

Erectile dysfunction and cardiovascular diseases

Reduced arginine-NO activity has been shown to play a role in the pathology of erectile dysfunction (4). Many studies have been conducted on erectile dysfunction, particularly among older men where this problem is more common as shown in Figure 1 (“ED” stands for “erectile dysfunction”) (2).

There is a link between erectile dysfunction and cardiovascular diseases. Ischemic heart diseases are heart diseases caused by limited blood supply to the heart. This is usually caused by narrowing of vessels. This can have the same cause as erectile dysfunction, namely the aforementioned reduced arginine-NO activity (5). As many as 75% of men with ischemic heart disease suffer from erectile dysfunction!(6).

The effect of arginine on the erection according to research

Now that we know the (physiological) functioning of an erection, it’s easier to understand the studies done on the effect of arginine on an erection. Arginine is interesting to science in this regard as a “precursor” (substance that can be converted into another substance) of NO (2, 7). The studies on this show, as is often the case, different results, although most show a positive result. Although various studies have been done on the effect of arginine on the erection of animals such as rats and dogs, I will limit myself here to the studies among humans.

“2.8 grams of arginine per day improves erection”

In 1994, a small group of men participated in a study in New York where they received 2.8 grams of arginine per day for two weeks. Unfortunately, I can’t elaborate on this but only present the summary since the full text is not available. Forty percent of the men reported “an improvement.” However, the (degree of) erectile dysfunction was not formally established beforehand (8).

“5 grams of arginine per day improves sexual function”

In a study where that had been done, moreover, the number of participants was larger (50 men) and was carried out “double-blind” (9). The group was thus divided into two, where one group received arginine and the other group a placebo for control. In this case, the period was six weeks in which they received 5 grams of arginine per day or a placebo. Of the 29 men who received arginine, nine (31%) reported positive effects regarding sexual function. When the researchers then looked at the amount of NO in the urine (as an indication of NO production/release), the positive effect only applied to men whose NO production/release was low.

Oral administration of L-arginine in high doses seems to cause significant subjective improvement in sexual function in men with organic ED only if they have decreased NOx excretion or production.

-J. Chen, Tel Aviv University

From this, you could infer that arginine only has a positive effect on erection when the amount of NO, or its activity, is reduced. In this sense, it resembles creatine, which also has no effect on people who naturally already have the maximum amount. With creatine, however, the tricky part is that you only find this out by having it tested in a lab. When it comes to a potential added value of arginine on an erection, you have the “advantage” that the symptoms of an NO deficiency are clearer.

1.5 grams of arginine per day has no effect

German researchers divided 32 patients with an average age of almost 52 years into two groups (10). One group received three times daily 0.5 grams of arginine, the other group a placebo. At the end of the 17 days, a “washout” period of seven days followed before the groups were switched (so the effects of the first 17 days had no influence on the second period of 17 days). Of the 30 men who ultimately completed the study, an equal number noticed improvement after taking arginine as men who noticed improvement after taking the placebo. The researchers thus concluded that arginine is no better than a placebo.

Oral L-arginine 3 x 500 mg/day is not better than placebo as a first-line treatment for mixed-type impotence.

-T. Klotz, University of Cologne

Caveats about arginine against erectile dysfunction

Two caveats must be made about this last study. Firstly, the amount of arginine used for this study is smaller than for the previously mentioned studies (1.5 grams compared to 2.8 and 5 grams per day). In addition, they speak of mixed-type impotence while it seems that especially erectile dysfunction due to problems with NO production and release can benefit from intake of arginine.

That not every erectile dysfunction is caused by a lack of NO or its precursors such as arginine, is evident, among other things, from the fact that people with ischemic heart complaints do not always suffer from erectile dysfunction, “only” the previously mentioned 75%. Conversely, not everyone with erectile dysfunction suffers from ischemic heart complaints. This makes it clear that there can be other causes for erectile dysfunction than vascular constriction due to a lack of NO. If this were always the cause of erectile dysfunction, you would expect ischemic heart complaints in all those cases.

You may wonder what the cause of the impotence was in the men from the German study.

If arginine works, then it works in a more natural way upon arousal

Although arginine must yield in effectiveness to (active ingredients of) popular drugs like Viagra and Cialis, it does have an advantage over these drugs. Arginine works, if it works, in a more natural way. The only thing that changes is that there is more arginine available to be converted into NO. For this conversion, arousal is still necessary, which ensures that the nerves initiate the process as previously described (Arousal –>nervous system–>NO (produced from arginine)–>GC–>GTP–>cGMP–>erection). Here, use is made of the previously replenished arginine supply.

In the case of PDE5 inhibitors like Viagra, the influence occurs at a completely different point, namely the moment when the important cGMP is broken down into the inactive GMP. However, this requires good timing while arginine is simply taken daily to build up a larger stock. Taking Viagra an hour in advance may not be a problem in a stable relationship with an understanding partner, but it can be more difficult if you unexpectedly do have success in the nightlife. Suddenly, you have to spend an hour talking about trivial things while waiting for something to happen “down there.”

Very simply put, you can compare it to attaching a water balloon to a tap that you let drip. At the bottom of the balloon is a hole. The dripping water represents the blood that flows into the penis while the hole represents the breakdown of cGMP leading to the blood flowing out. Using arginine ensures that the tap can be opened wider so that more water flows in than flows out through the hole. This allows the balloon to fill up quickly. PDE5 inhibitors such as Viagra can be seen as plugging the hole at the bottom. Since the water still drips in slowly, you need an hour before the balloon is tense. You can then also understand why in some cases such an erection can last undesirably long. When the arousal stops, the dripping of water into the balloon also stops, but as long as the hole at the bottom is closed, the balloon will remain tense.

Studies on the effect of arginine in combination with other substances

It often happens that two, three, or more substances are tested together. There are also studies that looked at combinations:

• Arginine and N-omega-nitro-L-arginine methyl ester (11)
• Yohimbine tartrate and l-arginine glutamate (12)
• Arginine and Pycnogenol (13)
• Arginine, propionyl-L-carnitine, and niacin (14,15)

This makes it difficult to determine the effectiveness of one of those substances, especially because they are tested together to examine their interaction (is the joint effect more than the sum of the parts?). These studies are mainly done to then be able to sell erection-enhancing drugs with these substances as ingredients. Pycnogenol, for example, is the brand name of a product made from the bark of pine trees (16). You may then wonder how objectively those studies are conducted. I will not discuss these studies for both reasons, although they all showed positive results.

The effect of citrulline on (getting) an erection

Citrulline’s effect on erection is more interesting. In “What is arginine?” I already wrote that citrulline might be even more interesting than arginine because it is converted into arginine in the body while arginine itself is largely broken down before reaching the bloodstream after oral intake. Thus, the same positive effects of arginine would be expected from citrulline, possibly even more since citrulline might lead to more arginine in the blood than intake of arginine itself. Various studies have been done on this.

Italian researchers gave 24 men with “a mild to normal form of erectile dysfunction” 1.5 grams of citrulline or a placebo per day (17). When they received citrulline, half of the men reported that their “erection hardness score” went up from 3 (“mild erectile dysfunction”) to 4 (“normal erection”). When the same group received a placebo, only 2 reported this.

Although less effective than phosphodiesterase type-5 enzyme inhibitors, at least in the short term, L-citrulline supplementation has been proved to be safe and psychologically well accepted by patients. Its role as an alternative treatment for mild to moderate ED, particularly in patients with a psychologically fear of phosphodiesterase type-5 enzyme inhibitors, deserves further research.

-L. Cormio, University of Foggia

Last year, two different studies also showed positive effects of citrulline on the erection of rats (these animal studies are mentioned here because otherwise, there is only one study that is not confirmed/disproved) (18,19).

It’s unfortunate that arginine and citrulline were not compared directly. It is noteworthy, however, that in this case, 1.5 grams of citrulline does have an effect where 1.5 grams of arginine, as used by the German researchers as the only study, showed no positive result. Possibly, too little of the 1.5 grams of arginine remains after breakdown for effect. This difference could also lie in the subjects used. Perhaps there were more men among the Italians whose erectile dysfunction was caused by a deficiency in NO production/release.

Conclusion

The conclusion can be kept short. Arginine and citrulline can have a positive effect on the erection of men. This is possibly only, or stronger, in those cases where reduced function of the erection is caused by lowered Arginine-NO production/release. This effect is potentially (literally and figuratively) not comparable to that of products like Viagra and Cialis but works in a more natural manner.

References

1. Goldstein I. Male sexual circuitry. Working Group for the Study of Central Mechanisms in Erectile Dysfunction. Sci Am 2000;283:70-75
2. McKay D. Nutrients and botanicals for erectile dysfunction: examining the evidence. Altern Med Rev. 2004 Mar;9(1):4-16.
3. Bouman, L.N., Bernards, J.A.m Boddeke, H.W.G.M.,Medical Physiology
4. Gonzalez-Cadavid NF, Rajfer J. Therapeutic stimulation of penile nitric oxide synthase (NOS) and related pathways. Drugs Today (Barc) 2000;36:163-174.
5. Sullivan ME, Thompson CS, Dashwood MR, et al. Nitric oxide and penile erection: is erectile dysfunction another manifestation of vascular disease? Cardiovasc Res 1999;43:658-665.
6. Kloner RA, Mullin SH, Shook T, et al. Erectile dysfunction in the cardiac patient: how common and should we treat? J Urol 2003;170:S46-S50.
7. Melman A.This month in investigative urology. L-arginine and penile erection.J Urol. 1997 Sep;158(3 Pt 1):686.
8. Zorgniotti AW, Lizza EF. Effect of large doses of the nitric oxide precursor, L-arginine, on erectile dysfunction. Int J Impot Res 1994;6:33-35.
9. Chen J, Wollman Y, Chernichovsky T, et al. Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study. BJU Int 1999;83:269-273.
10. Klotz T, Mathers MJ, Braun M, et al. Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study. Urol Int 1999;63:220-223.
11. Moody JA1, Vernet D, Laidlaw S, Rajfer J, Gonzalez-Cadavid NF. Effects of long-term oral administration of L-arginine on the rat erectile response. J Urol. 1997 Sep;158(3 Pt 1):942-7.
12. Kernohan AF1, McIntyre M, Hughes DM, Tam SW, Worcel M, Reid JL. An oral yohimbine/L-arginine combination (NMI 861) for the treatment of male erectile dysfunction: a pharmacokinetic, pharmacodynamic and interaction study with intravenous nitroglycerine in healthy male subjects. Br J Clin Pharmacol. 2005 Jan;59(1):85-93.
13. Stanislavov R1, Nikolova V. Treatment of erectile dysfunction with pycnogenol and L-arginine. J Sex Marital Ther. 2003 May-Jun;29(3):207-13.
14. Gianfrilli D1, Lauretta R, Di Dato C, Graziadio C, Pozza C, De Larichaudy J, Giannetta E, Isidori AM, Lenzi A. Propionyl-L-carnitine, L-arginine and niacin in sexual medicine: a nutraceutical approach to erectile dysfunction. Andrologia. 2012 May;44 Suppl 1:600-4. doi: 10.1111/j.1439-0272.2011.01234.x. Epub 2011 Oct 4.
15. Gentile V1, Antonini G, Antonella Bertozzi M, Dinelli N, Rizzo C, Ashraf Virmani M, Koverech A. Effect of propionyl-L-carnitine, L-arginine and nicotinic acid on the efficacy of vardenafil in the treatment of erectile dysfunction in diabetes.
16. http://www.nlm.nih.gov/medlineplus/druginfo/natural/1019.html
17. Cormio L1, De Siati M, Lorusso F, Selvaggio O, Mirabella L, Sanguedolce F, Carrieri G. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. 2011 Jan;77(1):119-22. doi: 10.1016/j.urology.2010.08.028.
18. Shiota A1, Hotta Y, Kataoka T, Morita M, Maeda Y, Kimura K. Oral L-citrulline supplementation improves erectile function in rats with acute arteriogenic erectile dysfunction. J Sex Med. 2013 Oct;10(10):2423-9. doi: 10.1111/jsm.12260. Epub 2013 Jul 11.
19. Hotta Y1, Shiota A, Kataoka T, Motonari M, Maeda Y, Morita M, Kimura K. Oral l-citrulline supplementation improves erectile function and penile structure in castrated rats. Int J Urol. 2013 Dec 23. doi: 10.1111/iju.12362. [Epub ahead of print]
20. Cormio L1, De Siati M, Lorusso F, Selvaggio O, Mirabella L, Sanguedolce F, Carrieri G. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction. Urology. 2011 Jan;77(1):119-22. doi: 10.1016/j.urology.2010.08.028.