If you’re stumped and staring at the supplement aisle…wondering if you should choose arginine supplements or citrulline supplements, you’re not alone. It’s confusing. So, let’s spend a few moments combing through the research to see just how these supplements work so you can make the best choice for your body and budget.
Citrulline and the Urea Cycle
Citrulline is one of the three amino acids that take part in the urea cycle. When amino acids break down, they release ammonia. The urea cycle is responsible for converting this ammonia into nontoxic urea that can be eliminated from the body through urine.
The other two amino acids that are part of the urea cycle are ornithine and arginine. Citrulline, arginine, and ornithine have a cyclical relationship. Ornithine and ammonia merge to form citrulline. Citrulline is then converted into arginine in the kidneys. Arginine is metabolized to ornithine, which produces citrulline, which produces arginine, and so on and so forth.
What does this mean for nutritional purposes? That citrulline is an effective way to increase arginine concentration in the blood.
Take a look at the figure below, which schematically represents the urea cycle.
The urea cycle functions in the liver.
- Citrulline plays a key role as a precursor for the formation of arginine. Most arginine degradation results in the production of ornithine, with urea as a byproduct.
- Arginine can also serve as a precursor for the production of nitric oxide (NO) or creatine by less prominent reactions.
- Ornithine plays a role in the urea cycle by detoxifying the blood and clearing ammonia (NH3) in a reaction that produces citrulline.
- The conversion of ornithine to citrulline completes the urea cycle.
- The cycle results in the conversion of toxic ammonia into nontoxic urea for secretion in the urine, without any change in the amounts of citrulline, arginine, or ornithine.
Supplementing with citrulline causes a significant increase in the plasma concentrations of not only citrulline but also ornithine and arginine. The following figure shows the progressive increase in citrulline, arginine, and ornithine in response to taking citrulline supplements. Citrulline supplementation thus ensures adequate amounts of the main components of the urea cycle. The response is the same in young and older individuals.
Not only is arginine concentration increased by taking citrulline, so, too, is the production of nitric oxide. The production of NO is less in older individuals than in young, but the increase is significant in both groups.
Nitric oxide is a key vasodilator, which means it plays an important role in regulating the rate of blood flow to different areas of the body, including muscle. In the resting state, blood flow may not be affected by an increase in NO production, but in circumstances such as exercise or following ingestion, nutrients such as amino acids and an increase in NO production will amplify the normal increase in muscle blood flow.
Should I Take a Citrulline or Arginine Supplement?
Increasing your arginine levels has many health benefits, which is why arginine supplements have been popularly peddled for the last 50 years. However, arginine supplements don’t actually produce marked increases in blood arginine concentrations, because the liver is very effective in clearing absorbed arginine.
In contrast, liver uptake of citrulline is low—most absorbed citrulline is cleared by the kidneys, where it is converted to arginine and released into the blood. For this reason, it’s more beneficial to take citrulline supplements as a means of effectively increasing arginine levels. In addition, there are no adverse effects of citrulline consumption, whereas arginine consumption can cause gastrointestinal discomfort.
The Bottom Line
Citrulline supplementation can support urea cycle activity and promote the production of NO. In addition, citrulline helps boost arginine levels in the body for benefits like maximal muscle protein synthesis. Taking a citrulline supplement is preferable to taking an arginine supplement when it comes to increasing blood arginine concentration, although consumption of arginine also has some benefits as well.