Citrulline (L-citrulline) is a non-essential amino acid that is converted into l-arginine (another type of amino acid) in the kidneys after supplementation.
It is known to improve blood flow, help people with heart disease and clogged arteries and improve erectile dysfunction.
It’s found in several testosterone boosters.
Citrulline is naturally made in the body. While most people make enough of it, some people benefit from supplementation. L-citrulline supplementation has been shown to be a more effective method of increasing L-arginine levels in the body than L-arginine supplementation itself. Unlike L-arginine supplementation that causes a spike of L-arginine in plasma, L-citrulline increases arginine plasma levels over a longer period of time.
Citrulline improves mild erectile dysfunction. L-citrulline has been shown to be a pro-erectile agent due to its ability to first be converted into L-arginine and then into nitric oxide — a gas that helps to dilate blood vessels. One of the main causes of erectile dysfunction is a decrease in blood flow to the penis.
In a study published in Urology in 2011, 24 men with mild erectile dysfunction (erection hardness score of three) were given a placebo for one month and L-citrulline, 1.5 g per day, for another month.
At the end of the study, erection hardness score, number of sexual relations per month, treatment satisfaction and adverse events were recorded. Researchers reported that an improvement in the erection hardness score from a three to four (normal erectile function) occurred in 50 percent of the men, compared to 8.3 percent who received a placebo.
The mean number of sexual relations per month also modestly increased and none of the participants reported experiencing adverse effects (2).
The researchers concluded that while L-citrulline is less effective (at least in the short term) than phosphodiesterase type-5 enzyme inhibitors — drugs approved for the treatment of erectile dysfunction — its safety record has caught the attention of many in the medical community as a possible alternative.
Oral supplementation of citrulline provides cardiovascular benefits. According to the CDC, approximately 5.7 million adults in the U.S. have heart failure (3). Researchers in 2010 set out to evaluate the efficacy of L-citrulline supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction (HFpEF) —a condition in which the heart pumps normally but is too stiff to fill properly (4).
A randomized clinical trial was performed on chronic outstanding and stable patients with HFpEF. The main findings were a significant decrease in pulmonary artery pressure in the citrulline group as well as improved right ventricular function (5). Diastolic and systolic artery pressure also decreased significantly.
Citrulline improves arterial stiffness. In another study published in the International Journal of Cardiology in 2012, researchers examined the short-term effects of L-citrulline on arterial stiffness in humans. Stiffening of the arteries is a hallmark of aging and contributes to a range of diseases, including cardiovascular disease, diabetes, stroke atherosclerosis and chronic renal disease (6).
Fifteen male subjects were given 5.6g daily of L-citrulline or placebo for seven days. Compared to the placebo group, short-term use of L-citrulline resulted in improved arterial stiffness.
There were no significant differences in blood pressure in either group. Researchers concluded that short-term L-citrulline supplementation may functionally improve arterial stiffness, independent of blood pressure.
Citrulline supplementation may be effective in reducing postoperative pulmonary hypertension. Forty children undergoing cardiopulmonary bypass were evaluated to determine whether citrulline supplementation was effective in decreasing the risk of postoperative pulmonary hypertension.
The children were randomized to receive five doses of either oral citrulline or placebo. The results published in The Journal of Thoracic and Cardiovascular Surgery, revealed several positive outcomes; Median citrulline concentrations were significantly higher in the citrulline group versus the placebo group immediately post-op and at 12 hours post-op.
In addition, mean plasma arginine concentrations were significantly higher in the citrulline group versus the placebo group by 12 hours postoperatively.
Post-op pulmonary hypertension did not occur in children with naturally elevated citrulline levels or elevations through supplementation (7).
Citrulline may help individuals with prehypertension. Nitric oxide is a key signaling messenger in the cardiovascular system. It acts as a vasodilator that relaxes the arteries for better blood flow and is a main regulator of arterial blood pressure (8). A team of researchers evaluated the effects of citrulline supplementation on aortic blood pressure and arterial function in nine individuals with prehypertension.
After six weeks of supplementation, it was concluded that citrulline improved aortic blood pressure in middle-aged adults with prehypertension.
In addition, supplementation was well tolerated by all subjects, with no adverse effects reported.
Citrulline shows promise in boosting immunity. Evidence has been mounting over the past several years showing that arginine and citrulline pack a one-two punch when it comes to initiating an immune response. Studies have shown that arginine and citrulline deficiencies may underlie the detrimental outcome of inflammatory conditions, such as sepsis (9).
As a result, strategies to improve the arginine availability during inflammatory conditions have gathered widespread attention over the past decades. In a review of available literature, authors concluded in the March 2015 issue of Nutrients that maintaining the arginine availability during inflammatory conditions is crucial and probably best achieved by enhancing the citrulline concentration and maintaining adequate enzyme function during these conditions.
Future studies are needed to determine whether or not a deficiency in arginine is present in other inflammatory conditions as well as the safety of supplementation (10).
There have been no reported side effects with use of citrulline and it appears to be safe.
However, L-citrulline supplementation may affect how other drugs work in the body and should not be taken by those who are taking nitrates for heart disease, erectile dysfunction drugs (such as Cialis, Viagra and Levitra) or medication to lower blood pressure. Taking this supplement while on these medications can cause a dangerous drop in blood pressure (11).
The suggested dosage for L-citrulline depends on what disease is being treated or prevented; according to some sources, the typical dose is six to nine grams daily, divided throughout the day.
As with any supplement or medication, consult with your doctor before taking L-citrulline supplements.
L-citrulline is a non-essential amino acid that is converted into L-arginine in the kidneys after supplementation. The primary benefits of this supplement include improving blood flow, helping people with heart disease and clogged arteries and improving erectile dysfunction.
Researchers are also studying its efficacy in reducing postoperative pulmonary hypertension, treating individuals with prehypertension and possibly boosting immunity.
Citrulline is considered to be safe when taken properly, but should not be taken by those taking nitrates for heart disease, erectile dysfunction drugs or medication to lower blood pressure.