What is citrulline?

L-citrulline is one of the three dietary amino acids in the urea cycle, alongside L-arginine and L-Ornithine. Taking L-citrulline increases plasma levels of ornithine and arginine and improves the ammonia recycling process and nitric oxide metabolism. Consequently, it is used in areas where nitric oxide is relevant, namely athletic performance, and vascular health, and erectile dysfunction. There are very few foods that have notable amounts of citrulline, watermelon being a notable exception.

What are citrulline's benefits?

In general, much research suggests a modest reduction in blood pressure and improvement in blood flow from chronic citrulline supplementation, particularly for those with hypertension and other cardiovascular problems. Limited research suggests an improvement in power output, a reduction in fatigue and improved endurance for both aerobic and anaerobic exercise. Many of the studies have used acute citrulline supplementation, and it's possible that there's an effect there, but benefits are more likely to be found from chronic supplementation. More research for erectile dysfunction but a small amount of research is supportive of a beneficial effect. There's more positive research for arginine, and citrulline increases arginine levels so it's plausible that it's also effective for this purpose.

What are citrulline's side effects and drawbacks?

It's not known to have notable side-effects, though more research is needed to confirm its long-term safety when taken in high doses. Unlike L-arginine and L-ornithine, very high doses don't seem to result in gastrointestinal upset.

Is arginine or citrulline better?

A small amount of research suggests that taking citrulline will lead to higher and more consistent arginine levels than taking arginine. Citrulline is very readily converted to arginine as needed, and it is also better absorbed than arginine, which not only makes it a better source of arginine for the body but can mean a lower rate of gastrointestinal upset than arginine when taken in high doses.

What is citrulline malate?

Citrulline bound to malate, an organic salt of malic acid, an intermediate in the citric acid cycle. It is the most researched form of citrulline, and there is speculation about an independent role of malate in producing performance benefits, but there's insufficient research to compare citrulline malate to L-citrulline directly. Citrulline malate can be taken in the dose used in studies, but it's important to keep in mind that 1.76 g of citrulline malate is needed to about 1 g of citrulline.


My experience: Citrulline far outperforms arginine and agmatine as far as nitric oxide production as well as growth hormone stimulation. The pumps are second to none for over the counter supplements and when combined with viagra, levitra or other ED medications (ask your doctor first) it provides the most blissfully painful and skin splitting pumps I’ve ever felt before. It’s my #1 favorite supplement and probably always will be.

Why stack with viagra?

This and other ED treatments work by creating more nitric oxide just as Citrulline does but in a different way. The body has an enzyme that inhibits nitric oxide production because it doesn’t want levels to get too high. Viagra works by inhibiting the enzyme that governs nitric oxide levels. So Citrulline alone will help but it has a cut off point. By adding viagra, etc. you are allowing your body to make larger amounts of nitric oxide than you could without it.



https://www.accessdata.fda.gov/drugs...895s033lbl.pdf

CLINICAL PHARMACOLOGY

Mechanism of Action

The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation.
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Studies in vitro have shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases (10-fold for PDE6, >80-fold for PDE1, >700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). The approximately 4,000-fold selectivity for PDE5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility. Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina which is involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels (see Pharmacodynamics).
In addition to human corpus cavernosum smooth muscle, PDE5 is also found in lower concentrations in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle. The inhibition of PDE5 in these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of nitric oxide observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo.

https://www.accessdata.fda.gov/drugs...895s033lbl.pdf


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