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Citrulline, Nitric Oxide, Erectile Dysfunction & PDE5 Inhibitors

Citrulline use as a 'masked' L-Arginine generator

Citrulline is a far better way of generating L-Arginine than using L-Arginine itself, which is the precursor amino acid leading to the formation of Nitric Oxide (NO).

Nitric Oxide (NO) is a powerful vasodilator, i.e. it widens the diameter of blood vessels allowing more blood to be transported through a wider channel and this, in turn, allows more oxygen and nutrients to be delivered to tissues such as the heart or skeletal muscle with exercise.

So why take Citrulline rather than L-Arginine? The reason is that L-Arginine is absorbed in the gastrointestinal tract and then transported to the liver where it undergoes rapid first-pass metabolism to other compounds leaving very little for the body to produce Nitric Oxide (NO)1.

Citrulline is essentially a ‘masked form’ of L-Arginine1. It is absorbed from the bloodstream and then transported to the kidneys where it is then converted to L-Arginine and distributed directly into the bloodstream to be used by muscles, tissues and blood vessels including the penile artery in men with erectile dysfunction.

Citrulline may be of great benefit to men with Erectile Dysfunction

Citrulline is a far better way of generating L-Arginine than using L-Arginine itself, which is the precursor amino acid leading to the formation of Nitric Oxide (NO).

Nitric Oxide (NO) is a powerful vasodilator, i.e. it widens the diameter of blood vessels allowing more blood to be transported through a wider channel and this, in turn, allows more oxygen and nutrients to be delivered to tissues such as the heart or skeletal muscle with exercise.

So why take Citrulline rather than L-Arginine? The reason is that L-Arginine is absorbed in the gastrointestinal tract and then transported to the liver where it undergoes rapid first-pass metabolism to other compounds leaving very little for the body to produce Nitric Oxide (NO)1.

Citrulline is essentially a ‘masked form’ of L-Arginine1. It is absorbed from the bloodstream and then transported to the kidneys where it is then converted to L-Arginine and distributed directly into the bloodstream to be used by muscles, tissues and blood vessels including the penile artery in men with erectile dysfunction.

Nitric Oxide plays a critical role in Erectile Dysfunction

Around 30 – 40% of men with erectile dysfunction (ED) do not respond to PDE5 inhibitors such as Viagra or Cialis. The reason is that these PDE5 inhibitors depend upon a sufficient amount of cGMP being produced as the PDE5 inhibitors prevent the breakdown of cGMP allowing this molecule to exert its vasodilatory effect in penile vascular tissue.

The Catch-22 here is that there needs to be enough cGMP being produced in the first place and this will only happen if Nitric Oxide is present in sufficient quantities to stimulate Soluble Guanylate Cyclase (sGC) which then converts GTP → cGMP.

So why do you need Nitric Oxide support?

Many factors from ageing, chronic diseases, vascular disease, inflammatory processes, oxidative stress can all result in either poor synthesis of Nitric Oxide or availability in the endothelium of blood vessels or release from nerve endings.

The common disease states that can lead to poor Nitric Oxide availability are – Erectile Dysfunction, Prediabetes, Diabetes, Hypertension, Hyperlipidaemia and existing Vascular Disease

Having enough L-Citrulline will lead to available L-Arginine which is then converted to Nitric Oxide to facilitation vasodilation and an erection.

Supporting supplements:

  1. DHA  + Choline – to support cell membranes, decrease inflammation thus protecting Nitric Oxide
  2. N-Acetyl Cysteine – to generate Glutathione a powerful antioxidant to offset inflammation and oxidative stress and protect Nitric Oxide from being degraded

References:

  1. De Tejada, I.S., 2004. Therapeutic strategies for optimizing PDE-5 inhibitor therapy in patients with erectile dysfunction considered difficult or challenging to treat. International journal of impotence research, 16(S1), p.S40.
  2. Zorgniotti, A.W. and Lizza, E.F., 1994. Effect of large doses of the nitric oxide precursor, L-Arginine, on erectile dysfunction. International Journal of Impotence Research, 6(1), p33