What is Arginine?

Arginine is a naturally occurring substance.  Arginine belongs to a class of chemicals called amino acids.   Amino acids are the building blocks of proteins.  There are 22 amino acids that are joined together to form proteins in humans.

Arginine is also the chemical precursor of nitric oxide. Nitric oxide is the most important chemical messenger of the erection process. Nitric oxide is truly the “erection molecule”. Arginine is converted to nitric oxide by an enzyme called Nitric Oxide Synthase.

Nitric oxide stimulates a cascade of chemical reactions that ultimately produces dilation of the arteries to the penis.  This allows the penis to fill with blood which results in the erection.  This cascade of chemical reactions is called the Nitric Oxide Pathway.

Does Arginine Improve Erectile Dysfunction?

When arginine is given alone for the treatment of erectile dysfunction, it does not produce a significant improvement in erectile function.

When arginine is given in combination with other natural substances that stimulate the Nitric Oxide Pathway, the combination does improve erectile function. 

Studies of Arginine Alone For the Treatment of ED

One study performed in Germany showed that oral arginine was no better than a placebo for the treatment of ED.  Another study from Israel showed subjective, but little objective, improvement of the erection following treatment with arginine.

These two studies show that arginine alone is not effective for the treatment of ED.

Arginine Plus Cialis

There are several studies, however, that strongly suggest that arginine in combination with other substances does improve erectile function.

A recent study from Egypt was performed upon 108 diabetic men with erectile dysfunction.  Arginine plus Cialis produced superior erectile function compared to Cialis alone.  The authors concluded that the combination was effective because each component stimulates the Nitric Oxide Pathway in separate ways.

Arginine Plus Yohimbine

Yohimbine also stimulates the Nitric Oxide Pathway.  Yohimbine stimulates the conversion of arginine to nitric oxide.  This property makes yohimbine an ideal substance to combine with arginine.  The combination would likely lead to an increase in nitric oxide levels.

In order to test this hypothesis, two studies were performed.  One study from France and one study from Iran showed a significant improvement in erectile function with the combination of arginine and yohimbine.  The benefit from the combination was significantly greater than the benefit from each substance alone.

Arginine Plus Pycnogenol

A study from Italy involved 124 patients with erectile dysfunction.  They were treated with a combination of arginine and pycnogenol.  Pycnogenol stimulates the conversion of arginine to nitric oxide.  The combination produced a sharp improvement in erectile function. 

Arginine Plus Adenosine Monophosphate

A study performed in France used the combination of arginine and adenosine monophosphate to treat erectile dysfunction.  The combination resulted in a significant improvement in erectile function. 

Adenosine monophosphate does not affect the Nitric Oxide Pathway.  Instead, this substance leads to an increase in C–AMP.  C-AMP is a chemical messenger that directly stimulates the erection process.     

Side Effects of Arginine

Arginine has only a few mild side effects.  These include headache, GI upset, and a mild drop in blood pressure.  Arginine has far fewer side effects than does Viagra.  Up to 50% of patients who take Viagra report significant side effects. 

Arguments in Favor of Arginine for the Treatment of ED

The rationale for oral arginine supplementation is that it will lead to a rise in nitric oxide which in turn will stimulate the Nitric Oxide Pathway.  This pathway is directly responsible for the erection. 

There is also a strong rationale for combining Arginine with other natural substances that stimulate the Nitric Oxide Pathway in different ways.  This combination therapy shows a clear benefit in terms of erectile function.

Arguments Against the Use of Arginine for the Treatment of ED

The first problem is that much of the arginine that is consumed orally is broken down by the liver and the digestive system before it can be converted to nitric oxide.

The second problem is that even if oral arginine supplements increase blood arginine levels, this may not result in an increase in nitric oxide levels.  Just because the body can convert arginine to nitric oxide – it does not mean that the body will convert arginine to nitric oxide. It all depends upon the kinetics of the chemical reactions – which is a complex scientific problem. 

Whether vitamins and supplements stimulate these chemical processes is a critically important issue.  Supplements may be of benefit only if the patient is deficient in a particular chemical or vitamin. If a patient has normal levels of chemicals and vitamins, adding more to the body may not change anything.

Patients with ED Have Low Levels of Arginine

The findings of a recent study performed in 2017 provide interesting evidence in favor of arginine supplements.  This study evaluated arginine blood levels in patients with erectile dysfunction.  The results showed that patients with ED tend to have lower blood arginine levels than those without ED.  The results suggest that arginine supplements may correct an underlying arginine deficiency in patients with ED.

Conclusions About arginine for ED

Oral arginine alone is not effective as a first line therapy for the treatment of ED.  However, oral arginine when combined with other substances that influence the Nitric Oxide Pathway does show promise.

In addition, the side effects of arginine are minimal.  Viagra, however, produces significant side effects in up to 50% of patients. 

More studies of combination therapy with arginine are needed.

The Nitric Oxide Pathway

There are three important chemical steps involving the Nitric Oxide Pathway.  They are as follows:

  1. Arginine is converted to nitric oxide by an enzyme called Nitric Oxide Synthetase
  2. GTP is converted to c-GMP by an enzyme called Guanyl Cyclase. Nitric oxide stimulates this step.
  3. C-GMP is converted to 5 – GMP by an enzyme called 5 Phospho – Diesterase. 

Key Points of the Nitric Oxide Pathway

  1. Nitric Oxide is the key chemical messenger for the erection process. It is the “erection molecule”.
  2. Arginine is the direct precursor of nitric oxide
  3. C-GMP leads to the erection by dilating the penile artery and relaxing smooth muscle in the penis.
  4. C – GMP is completely inactivated when it is converted to 5-GMP.  Viagra blocks this conversion. Viagra causes a rise in C-GMP which produces the erection.

 

Sources:

  1. Klotz, T, Mathers, M, Braun, M, Bloch, W, Engelman, U, Effectiveness of Oral L-Arginine in First-Line Treatment of Erectile Dysfunction in a Controlled Crossover Study, Urologia Internationalis, 63, 220-223, 1999

  2. Chen, J, Wollman, Y, Chernichovsky, T, Iaina, A, Sofer,  M, Matzkin, H, Effect of Oral Administration of High Dose Nitric Oxide Donor L-Arginine in Men with Organic Erectile Dysfunction, British Journal of Urology, 83, 269-273

  3. Taieb, M, Hegazy, E, Ibrahim, A, Daily Oral L-Arginine Plus Tadalafil in Diabetic Patients with Erectile Dysfunction, The Journal of Sexual Medicine, 16, 1390-1397, 2019

  4. Lebret, T, Herve, J, Gorny, P, Worcel, M, Botto, H, Efficacy and Safety of a Novel Combination of L-Arginine Glutamate and Yohimbine Hydrochloride: A New Oral Therapy for Erectile Dysfunction, European Urology, 41, 609-613, 2002

  5. Akhondzadeh, S, Amiri, A, Bagheri, A, Efficacy and Safety of Oral Combination Of Yohimbine and L-Arginine for the Treatment of Erectile Dysfunction, Iranian Journal of Psychiatry, 5, 1-3, 2010

  6. Ledda, A, Belcaro, G, Cesarone, M, Dugall, M, Schonlau, F, Investigation of a Complex Plant Extract for Mild to Moderate Erectile Dysfunction, BJU International, 106, 1030-1033

  7. Neuzillet, Y, Hupertan, V, Cour, F, Botto, H, Lebret, T, A Randomized Double Blind Crossovre Placebo Controlled Comparative Clinical Trial of Arginine Aspartate Plus Adenosine Monophosphate for the Intermittent Treatment of Male Erectile Dysfunction, Andrology, 1, 223-228, 2013

  8. Barassi, A, Romanelli, M, Pezzilli, R, Damele, C, Vaccalluzzo,  L, Goi, G, Papini, N, Colpi, G, Massaccesi, L, Melzi d’ERil, G, Levels of L-Arginine and L-Citrulline in Patients with Erectile Dysfunction of Different Etiology, Andrology, 5, 256-261, 2017