What Is Citrulline?
This article discusses citrulline and its various benefits including physical performance, cardiovascular health, erectile dysfunction, and Sickle cell disease.

What Is Citrulline?

By Sherry Christiansen | Updated on March 20, 2021
Medically reviewed by Arno Kroner, DAOM, LAc

Citrulline is a natural supplement that is considered a non-essential amino acid. This means that the body can make its own citrulline; it can also be found in some foods (such as watermelon). Citrulline is synthesized (made) in the liver and intestine; its function is to detoxify ammonia and act as a vasodilator (dilating the blood vessels). Citrulline is also said to have an antioxidant effect.

There are two forms of citrulline, available as a supplement; these include L-citrulline and citrulline malate. The primary difference between the two types of citrulline is that L-citrulline is simply citrulline without any other substance, and citrulline malate is comprised of L-citrulline, plus DL-malate (a compound that may be instrumental in converting food to energy.)


What Is Citrulline Used For?

Although there is very little scientific research evidence to back many of the claims of L-citrulline health benefits, the natural supplement is said to have several health promoting properties, and is used for health conditions, including:

  • Enhancing physical exercise
  • Improving athletic performance
  • Helping with erectile dysfunction
  • Lowering high blood pressure
  • Treating sickle cell anemia



Athletic Performance

A 2010 randomized double-blind study (the gold standard of research studies) involving 41 men, discovered that a single dose of citrulline malate (CM) resulted in a significant increase in the number of barbell bench presses (accounting for 52.92% more repetitions) and a 40% decrease in muscle soreness after exercise. “We conclude that the use of CM might be useful to increase athletic performance in high-intensity anaerobic exercises with short rest times and to relieve post exercise muscle soreness,” wrote the study authors.

Another study, published in 2017, looking at older individuals found citrulline modestly increased muscle blood flow during submaximal exercise in men but not women. The same study found that the diastolic blood pressure of the treated group was lowered in men but not women.

Cardiovascular (Heart and Blood Vessel) Health

Studies have shown that short-term L-citrullline supplementation can lower blood pressure in adults with hypertension (high blood pressure) and those with pre-hypertension. These studies suggest that pharmaceutical/nutraceutical grade L-citrulline was instrumental in promoting heart health. “The safety and efficacy of long-term l-citrulline supplementation therefore requires further investigation,” concluded the study authors.

A paper published in 2019 reviewed 8 trials looking at adults. Their analysis of the data suggested citrulline can lower systolic blood pressure (by 4 mmHg). A significant decrease in diastolic blood pressure was seen only at higher doses. The authors felt it was too soon to recommend citulline supplements but that a diet rich in citrulline containing foods might contribute to the prevention of hypertension.

It’s important to note that there are several other (less potent) grades of supplements of which may be less effective (such as medical grade, nutritional grade, and cosmetic grade). Pharmaceutical grade must be more than 99% pure (from natural sources) and must contain no dyes, filler, binder or unknown substances.

Erectile Dysfunction

L-citrulline is said to boost L-arginine, which in turn helps to elevate nitrogen oxide (NO) synthesis. NO promotes the relaxation of blood vessels, resulting in oxygen-rich blood circulating through the arteries. Therefore, L-arginine is said to promote heart health, but it is also important in erectile function (because of its blood flow promotion properties).

In a study of 24 participants from the age of 56 to 66, the use of L-citrulline was found to improve the erection score from 3 (mild erectile dysfunction) to 4 (normal erectile function) in 50% of the men who took it, as compared to improvement in 8.3% of the men who took a placebo.

The study authors concluded, “Although less effective than phosphodiesterase type-5 enzyme inhibitors [such as Viagra], at least in the short term, L-citrulline supplementation has been proved to be safe and psychologically well accepted by patients. Its role as an alternative treatment for mild to moderate ED, particularly in patients with a psychological fear of phosphodiesterase type-5 enzyme inhibitors, deserves further research.”

Sickle Cell Disease

Studies have shown that some symptoms of sickle cell disease may be alleviated by taking a twice daily dose of L-citrulline by mouth. Not only was blood health improved with the administration of citrulline, study subjects also realized an improvement in overall well-being.5

A double-blind clinical research study involving study participants with sickle cell anemia (SCA) discovered a link between an increased level of NO and a decrease in the frequency that the study subjects experienced pain. L-citrulline is thought to promote an increase in the level of NO in the body, as well as promoting L-arginine levels. This study found that L-arginine supplementation may serve to potentiate the treatment of sickle cell anemia, but the study authors explained that more research is needed to evaluate the long-term safety and efficacy of these natural supplements.

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