Citrulline is commonly included in NO (nitric ocide) supplements. Citrulline is a non-essential, non-protein amino acid that plays a role in the urea cycle, which is responsible for detoxifing and excrete excess ammonia produced when amino acids are broken down in order to prevent a toxic level being reached.

Citrulline is converted into arginine in the urea cycle, but it is not interchangeable with arginine, which is also usually included in NO supplements. This is because constant use of arginine supplements can lead to increased arginase expression, which means arginine is broken down faster. Citrul;ine does not have the same effect. Instead nitric oxide synthase (NOS) regenerates citrulline while converting arginine into nitric oxide. Thus citrulline has a longer half-life allowing for more arginine to last longer in the body. Thus citrulline is a better source of arginine than actual arginine and when used together with arginine it improves NO production and blood flow.

Citrulline might prove effective for therapeutic purposes. Currently clinical trials are using it to see if it can help prevent hepatic venoocclusive disease (HVOD) and acute lung injury (ALI) in people undergoing chemotherapy for bone marrow transplantation. It is also being studied to see if it can help increase exercise tolerance in people suffering from Peripheral Arterial Disease (PAD).

Citrulline has been found to helpful in preventing post-operative hypertension as well as slowing the progression of atherosclerosis. Additionally, it seems to be safe to use at least in the short term in dosages as high as 15 grams.

As for healthy exercising people, citrulline supplementation can be helpful. For one, it helps deal with the increase in ammonia and lactic acid production that occurs when doing intense exercise. Thus it helps improve resistance to muscle fatigue. This allows healthy people to exercise longer before feeling exhausted.

Citrulline malate might also improve cardio exercise by providing an increase in energy/stamina. However, this particular capability has not been researched much and might just be a placebo effect.

Citrulline malate is typically taken in 3 to 6 gram doses before a cardio workout, which is a much higher dose than what is present in NO supplements, although the citrulline content in NO supplements is sufficient for its supportive role. (Posted on 2/18/11)