L-citrulline is a naturally occurring nonessential amino acid that enhances the production of nitric oxide in your body. Citrulline is found in a variety of foods and is also available in supplement form.
People take citrulline supplements for better strength and stamina, to improve erectile dysfunction, and for heart health.
Studies have found that taking L-citrulline may be medically helpful for heart disease, high blood pressure, high cholesterol, cancer chemotherapy, Alzheimer’s and other forms of dementia, immune disorders, sickle cell anemia, and short bowel syndrome[*].
Blood tests involving citrulline are even used to diagnose certain medical conditions including rheumatoid arthritis and small bowel pathologies[*]. The lower your levels of citrulline, the higher the chance you have some of these conditions.
So what exactly is L-citrulline? How does it work, do you need l-citrulline supplementation, are there unwanted side effects? You’ll learn all of that and more in this guide to your favorite non-essential amino acid.
What is L-Citrulline?
L-citrulline is a non-essential amino acid, which means your body makes it on its own. That also suggests that eating citrulline isn’t really required — but, of course that isn’t the whole nutrition story.
Your body produces citrulline in your liver and intestines. About 90% of citrulline is generated from the amino acid glutamine, while the remaining 10% comes from the amino acid arginine.
Damage to the intestinal lining or depletion of glutamine can result in decreased levels of L-citrulline[*]. Low levels of citrulline are linked to inflammation, depression, erectile dysfunction, high blood pressure, and cardiovascular disease[*][*].
That’s why it’s important to get some of this amino acid from your diet or from supplementation.
Fun fact: The word citrulline is derived from the Latin citrullus, for watermelon. Fresh watermelons contain about 1.1 to 4.7 milligrams per gram of naturally occurring L-citrulline[*].
How L-Citrulline Works
L-citrulline plays a role in your body’s urea cycle along with the amino acids L-ornithine and L-arginine. In the urea cycle, your body converts toxic ammonia into the byproduct urea, then excretes it during urination.
When you eat citrulline in foods or take it as a supplement, your kidneys convert it to arginine[*][*]. L-arginine is a precursor to nitric oxide, which plays an essential role in the function of your heart, blood vessels, and immune system.
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8 Benefits and Uses of L-Citrulline
Most of the benefits of L-citrulline occur because it increases L-arginine and nitric oxide levels in your body[*]. Higher nitric oxide levels relax blood vessels, increase blood flow, and improve circulation[*].
Nitric oxide and nitric oxide synthase also affect the release of dopamine and serotonin, as well as the signaling effects of dopamine in your nervous system[*][*][*].
Here are 8 science-backed ways L-citrulline works in your body.
#1: Citrulline Increases Exercise Capacity
Citrulline increases your body’s ability to perform aerobic and anaerobic exercise. When you take L-citrulline, your body produces more energy via ATP (an energy production molecule) and recycles bicarbonates[*].
More ATP means better exercise performance, and recycling bicarbonates helps prevent your muscles from becoming acidic and fatigued.
L-citrulline improves ATP production through both the creatine phosphate and oxidative pathways, which is why it can enhance your performance and recovery during explosive as well as endurance activities[*][*].
Citrulline may also increase exercise performance by increasing the availability of amino acids in your blood. It also may reduce the amount of ammonia your body produces during exercise[*].
In studies of healthy men, citrulline allows them to do more repetitions of bench press as well as cycle faster[*][*].
In a study of 30 patients with heart failure, L-citrulline supplementation allowed them to sustain exercise on a treadmill longer[*].
In advanced resistance-trained men, 8 grams of citrulline malate (equivalent to 4 grams of L-citrulline) allowed the men to perform higher numbers of repetitions during all three exercises[*].
In a study of competitive female master tennis athletes, 8 grams of citrulline malate increased their maximal and average grip strength, as well as peak and explosive power, and the ability to sustain power output during tennis trials.[*]
A study of 15 women found that 8 grams of citrulline malate increased their performance on upper- and lower-body resistance exercises and reduced their perceived exertion levels[*].
Other studies, including a study of the effects of citrulline in healthy young men and women performing German Volume Training (10 sets of 10 repetitions) found no effect of L-citrulline on performance, but the authors speculated that it could be due to the lack of a “loading dose” in the days and weeks before the exercise test[*].
Rat studies offered promising results as well, with L-citrulline increasing muscle synthesis, improving muscle strength, and increasing skeletal muscle weight[*][*][*].
#2: Citrulline Decreases Fatigue and Muscle Soreness
During strenuous exercise, the buildup of ammonia and hydrogen ions is associated with muscular fatigue and soreness.
In a study of 18 young men who reported general fatigue prior to the study, L-citrulline helped in a couple of ways. Once, by reducing post-exercise fatigue, and two by increasing their levels of ATP (energy) during exercise[*].
Other studies examining the effects of citrulline in healthy people have also shown that it can reduce exercise-induced fatigue[*][*][*].
Findings in humans and rats indicate that L-citrulline can improve muscle protein synthesis, which can improve post-workout recovery and reduce muscle soreness[*][*].
#3: Citrulline Reduces Erectile Dysfunction
Nitric oxide is a vasodilator, meaning it improves blood flow in blood vessels throughout the body.
Vasodilation can improve symptoms of erectile dysfunction, especially when it is due to vascular problems. And men with erectile dysfunction tend to have lower blood levels of L-arginine and L-citrulline[*].
A study of 24 men 55 years old or older with erectile dysfunction showed that L-citrulline increased the hardness of their erections.[*] Some men taking citrulline reported a greater frequency of sex and higher levels of satisfaction.
In a case study of a man who experienced sexual dysfunction after stopping SSRI antidepressants, a supplement regimen including L-citrulline helped restore his sexual function after several months[*].
Studies in rats and mice also show that citrulline supplementation can be effective in treating erectile dysfunction[*][*].
#4: Citrulline Lowers Blood Pressure
L-citrulline increases blood levels of L-arginine and nitric oxide. The vasodilating effect of nitric oxide production can lower blood pressure by causing blood vessels to dilate.
Three separate studies of young men found that taking citrulline leads to increases in nitric oxide and decreases in systolic and diastolic blood pressure, even during periods of stress[*][*][*].
In older men, but not older women, 6 grams per day of citrulline lowered diastolic blood pressure[*].
#5: Citrulline Improves Cardiovascular Health
Studies of heart failure patients demonstrate that L-citrulline can improve the health of the endothelium (the lining of blood vessels) as well as left and right ventricular function[*][*][*].
Thirty heart failure patients experienced an increase in exercise capacity after taking L-citrulline.[*]
Another study suggests that oral L-citrulline may help improve peripheral tissue oxygenation in heart failure patients, which can reduce complications from cardiovascular disease[*].
In rats fed an atherogenic (inflammatory to the cardiovascular system) diet, watermelon and L-arginine supplementation improved their cholesterol and lipid levels, reduced inflammation, and lowered oxidative stress[*].
L-citrulline may also protect heart cells by altering gene expression and enhancing the antioxidant capacity of the heart[*].
In obese and diabetic mice and rats, L-citrulline suppressed appetite and decreased food intake, resulting in fat loss. Citrulline may help reverse the cardiovascular risk factors of insulin resistance, overeating, and being overweight or obese[*].
L-citrulline therapy in rats reduced levels of asymmetric dimethylarginine (ADMA), a heart toxic compound that can lead to high blood pressure as well as cardiovascular disease[*].
#6: Citrulline Decreases Inflammation and Increases Antioxidants
By raising nitric oxide levels, increasing antioxidant levels, and improving blood flow and cellular function, citrulline may reduce inflammation and improve health, especially in older people or people with certain health problems.
According to the authors of a study on citrulline treatment in male aged rats, the ability of citrulline to protect against lipid oxidation may help slow or prevent the aging process[*].
Rats fed watermelon powder, which contains citrulline, had lower levels of inflammation, less oxidative DNA damage, and enhanced DNA repair through enzyme expression[*]. Citrulline may also reduce the risk of colon cancer through these mechanisms[*].
In old rats, citrulline helped to counteract the adverse effects of white adipose tissue on inflammation and metabolism[*].
In children with cellular damage caused by radioactive contamination, citrulline treatment improved the function of their endothelium (the smooth cells lining blood vessels) and reduced inflammation[*].
#7: Citrulline Raises Growth Hormone Levels
Citrulline increases arginine levels, and arginine can increase the release of growth hormone by suppressing somatostatin, a hormone that inhibits release of growth hormone[*].
A study of 17 competitive cyclists found L-citrulline supplementation increased growth hormone levels after rest, which can enhance your body’s repair and recovery processes[*].
#8: Citrulline May Act as an Antidepressant
By increasing nitric oxide, L-citrulline may enhance brain function, improve the health of cells in the brain, increase learning, and reduce depression[*]. Scientists have called endothelial nitric oxide the “protector of a healthy mind.”[*]
Studies have established a link between low levels of L-arginine and L-citrulline and the risk of depression[*].
People with major depression have lower levels of these amino acids[*]. Low levels of nitric oxide can also help to explain the link between major depression and cardiovascular disease[*][*].
According to one study, people with a diagnosis of bipolar disorder have reduced nitric oxide formation[*].
Disrupted nitric oxide signaling has also been linked in studies to neurodegeneration and the onset of dementia[*].
How to Get L-Citrulline
Unless you have a urea cycle disorder or damage to the lining of your intestines, your body makes L-citrulline from the amino acids L-glutamine, L-arginine, and L-ornithine.
Even if you are healthy, consuming extra citrulline in the form of food or supplements will increase nitric oxide levels, which can enhance your athletic performance and lead to health other benefits like the ones mentioned above.
Here’s how you can get a little more L-citrulline in your life.
Food Sources of L-Citrulline
Citrulline occurs naturally in some foods. Here are the most significant dietary sources of L-citrulline:
- Watermelon (red, yellow, and orange)
- Watermelon leaves
- Pumpkin leaves
- Chickpeas (not keto)
- Fish and meats
- Cacao and chocolate
Watermelon, the food richest in citrulline, provides up to 4.7 milligrams per gram of fresh watermelon. That means if you ate 500 grams (about 17.6 ounces) of watermelon, you could get up to 2.35 grams of L-citrulline.
However, 500 grams of watermelon is likely to put you over your carb limit for the day if you’re on a ketogenic or low-carb diet.
Other foods have lower concentrations of citrulline compared to watermelon, which is why food is not an efficient way to obtain extra citrulline.
Particularly if you are on a ketogenic diet, citrulline supplementation is a more effective way to obtain citrulline compared to eating fruits and other high-citrulline foods.
During prolonged workouts, Perfect Keto Perform pre-workout powder provides your body with the raw materials to maximize your training regimen and support an active lifestyle.
Perform contains the following ingredients:
- Beta-hydroxybutyrate: An exogenous ketone that can provide your body with energy in the absence of glucose
- Medium-chain triglycerides: Rapidly digested fatty acid your body converts to clean energy
- Branch chain amino acids: Supports muscle performance
- Creatine: Supports increased muscle output
- L-citrulline: Increases nitric oxide, delays muscle fatigue, and reduces soreness
- Beta-alanine: Supports muscle strength and increased power output
- Caffeine: From green tea, promotes prolonged alertness during workouts
Perfect Keto Perform’s synergistic blend is formulated to provide your body with the fuel you need for optimal performance during strenuous workouts.
L-Citrulline vs. L-Arginine
Citrulline increases arginine levels in your body, and both citrulline and arginine increase your body’s production of nitric oxide.
L-arginine is also available as a supplement, but oral L-citrulline is more effective than L-arginine supplements at increasing the levels of arginine in your blood[*].
Combining arginine and citrulline supplements increases nitric oxide more than either one alone[*][*].
Compared to arginine, citrulline supplements absorb more efficiently and then convert to arginine[*].
Is L-Citrulline Safe?
L-citrulline has a very low level of risk, and few studies have reported side effects. In two clinical trials, some people complained of upset stomach from taking citrulline[*][*].
According to a study in the British Journal of Nutrition, high doses of 15 grams of citrulline per day were safe and well-tolerated by the participants[*].
Because it increases nitric oxide levels, citrulline may affect the way some drugs work in your body. Talk to your doctor if you are taking any of the following medications:
- Blood pressure medication
- Erectile dysfunction drugs like Viagra or Cialis
- Nitrates for heart problems
It’s important to let your doctor know if you are taking any supplements so he or she can check for interactions with other medications.
If you are pregnant or breastfeeding, don’t use L-citrulline.
How Much L-Citrulline Should You Take?
Studies of citrulline show it can be taken one, two, or three times per day. Citrulline blood levels peak about an hour after you ingest it[*].
Take citrulline on an empty stomach 30 to 45 minutes before exercise. You can also take citrulline when you wake up and before you go to bed.
L-citrulline supplements can benefit you in different dosages, depending on your needs. Age, sex, and duration of use can also influence the effects of citrulline supplementation.
If you don’t experience benefits from taking L-citrulline, consider slowly increasing your dosage over time. Even taking doses of 15 grams of citrulline per day, you are unlikely to experience side effects[*].
For Athletic Performance and Energy
If you are using L-citrulline to improve your athletic performance and reduce fatigue, start with 3 to 6 grams per day of citrulline. Citrulline may work better after a loading phase of several weeks[*][*].
Doses of 6 to 8 grams citrulline malate, equivalent to 3-4 grams of L-citrulline, have been shown to increase athletic performance and exercise capacity in studies[*][*].
For Erectile Dysfunction
For treatment of erectile dysfunction, 1.5 grams per day of L-citrulline was effective in a study of older men[*].
To Reduce Fatigue
To reduce fatigue and increase exercise capacity, 2.4 grams per day of L-citrulline was effective in healthy men[*].
For Heart Health
In heart failure patients taking L-citrulline, 3 grams per day improved their right ventricular function and improved their treadmill endurance[*].
Three grams of L-citrulline per day was also effective in decreasing blood pressure in healthy young subjects.[*]
The Takeaway: Should You Take L-Citrulline?
L-Citrulline has a number of health benefits, from increasing physical performance to boosting heart health.
The most effective way to raise your L-citrulline levels is to take a supplement. Of course, be sure to talk to your doctor before you start any new supplement.
Have you tried L-citrulline? We’d love to hear about your experience in the comments below.