Citrulline: Benefits, Side Effects, Dosages, and Interactions


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 (like watermelon). Citrulline is synthesized (produced) in the liver and intestines; Its function is to eliminate ammonia toxins and act as a vasodilator (dilation of blood vessels). Citrulline is also said to have antioxidant effects .

There are two forms of citrulline available as supplements; these include L-citrulline and citrulline malate. The main difference between the two types of citrulline is that L-citrulline is just citrulline without any other substances, while citrulline malate is made up of L-citrulline plus DL-malate (a compound that can help convert food into energy. ).

Also know as

Citrulline (L-citrulline) is found under several other names, including:

  • 2-amino-5- (carbamoylamino) pentanoic acid
  • Citrulline malate
  • L-citrulline
  • L-citrulline malate
  • Citrulline Malat

What is citrulline used for?

While there is very little scientific evidence to support many of the health claims for L-citrulline, the natural supplement is believed to have several health-promoting properties and is used to treat conditions, including:


Athletic performance

A 2010 double-blind randomized study (the gold standard of research) in 41 men showed that a single dose of citrulline malate (CM) resulted in a significant increase in the number of bench presses (up to 52.92% more reps) and a decrease in muscle soreness after training by 40%. "We conclude that the use of CM may be beneficial in enhancing athletic performance in high intensity anaerobic exercise with short rest periods and in alleviating muscle soreness after exercise," the study authors write .

Another study published in 2017 in older adults found that citrulline slightly increased muscle blood flow during submaximal exercise in men, but not in women. The same study found that diastolic blood pressure in the treatment group was lowered in men but not in women.

Cardiovascular disease (heart and blood vessels)
Research has shown that short-term L-citrulline supplementation can lower blood pressure in adults with hypertension (high blood pressure) and in those with prehypertension. These studies indicate that pharmaceutical / nutraceutical grade L-citrulline has been shown to play an important role in promoting heart health. " Therefore, the safety and efficacy of long-term use of L-citrulline requires further study," the study authors concluded.

An article published in 2019 looked at 8 trials in adults. Their data analysis showed that citrulline can lower systolic blood pressure (by 4 mm Hg). A significant decrease in diastolic blood pressure was observed only at higher doses. The authors believe that it is too early to recommend citulline supplements, but that a diet rich in foods rich in citrulline can help prevent hypertension.

It is important to note that there are several other (less effective) supplements that may be less effective (for example, medical, nutritional, and cosmetic). Pharmaceutical grade must be greater than 99% pure (from natural sources) and free from colorants, fillers, binders, or unknown substances.

erectile dysfunction

L-citrulline is believed to enhance L-arginine, which in turn helps increase nitric oxide (NO) synthesis. NO promotes the relaxation of blood vessels, allowing oxygen-rich blood to circulate through the arteries. Therefore, L-Arginine is believed to promote heart health, but it is also important for erectile function (due to its blood flow promoting properties).

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

The study authors concluded: 'Although less effective than phosphodiesterase type 5 enzyme inhibitors [like Viagra], at least in the short term, L-citrulline supplementation was found to be safe and psychologically acceptable for patients. Its role as an alternative treatment for mild to moderate erectile dysfunction, especially in patients with psychological fear of phosphodiesterase type 5 inhibitors, deserves further investigation. "

Sickle cell anemia

Studies have shown that some of the symptoms of sickle cell anemia can be alleviated by taking an oral dose of L-citrulline twice a day. Citrulline intake not only improved blood health, but also improved the general well-being of the subjects .

A double-blind clinical study involving study participants with sickle cell anemia (SCA) found an association between increased NO levels and a decrease in how often subjects experienced pain. L-citrulline is believed to increase NO levels in the body and also increase L-arginine levels. This study showed that L-arginine supplementation can improve 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.

How does it work

In the body, L-citrulline is converted to another amino acid called L-arginine, which is converted to a chemical called nitric oxide. L-citrulline is believed to help supply the body with the raw materials it needs to make certain proteins. L-citrulline can also act as a vasodilator (a substance that dilates veins and arteries, helping to improve blood flow while lowering blood pressure).

Possible side effects.

Citrulline has been used as an oral (oral) supplement for many years, with no major safety concerns reported. Although citrulline side effects are rare, there have been reports of mild symptoms such as nausea, indigestion, and diarrhea.


A contraindication is a treatment, medication, or procedure (such as surgery) that is not recommended due to the high potential for harm to the patient. This means that under certain conditions (for example, during pregnancy), medications, supplements, or procedures should not be prescribed / performed. It can also indicate that two specific medications (including prescription drugs, over-the-counter drugs, and natural supplements) should not be prescribed together. Contraindications to L-citrulline include:

  • Pregnancy (there are not enough data from clinical trials to demonstrate the safety of citrulline during pregnancy).
  • Lactation (not enough clinical research data to support the safety of citrulline in lactation).

Those taking certain prescription medications should not take citrulline, these include:

  • Phosphodieterase-5 inhibitors (erectile dysfunction drugs such as Viagra and Levitra), because L-citrulline and phosphodieterase-5 inhibitors can lower blood pressure, and combining the two together can cause hypotension (high blood pressure). come down)
  • Nitrates (drugs that increase blood flow to the heart): Taking nitrates (often used to treat angina) along with citrulline can increase blood flow to the heart, which can cause side effects such as headaches, hot flashes , dizziness, fainting, blood pressure (hypotension) or irregular heart rhythms (arrhythmias). Nitrate-based drugs include dilatrate-SR and isordil (isosorbide dinitrate), ISMO (isosorbide mononitrate), and Nitro-Dur, Nitrolingual, or Nitrostat (nitrogylcerin).
  • Antihypertensive medications (high blood pressure medications) such as Norvasc or Lotrel (amlodipine), Cardizem CD, Cardizem SR, Dilacor XR or Tiazac (diltiazem), Calan SR (verapamil), HydroDIURIL (hydrochlorothiazide), Lasix (furosemide), and others. .. …

Other prescription drugs can interact with citrulline and this can negatively affect certain clinical conditions (such as those associated with hypotension), so its possible use should be discussed with your doctor.

The FDA notes that safety data is limited, so safety concerns cannot be ruled out.

Get Drug Information / Anastasia Tretyak

Preparation and dosage


L-citrulline is generally available in a powder form that can be mixed with liquid or added to food smoothies.

To improve performance, the average dose is 2 to 5 grams of L-citrulline per day. Studies have shown that you can take 3 to 6 grams per day of L-citrulline and 8 grams of citrulline malate without any side effects. In fact, a study from France found that taking up to 15 grams of citrulline was safe and well tolerated by study participants. No side effects were reported even when additional citrulline malate doses of up to 20 grams were taken .

What to look for

Natural supplements (such as citrulline) are not regulated by the Food and Drug Administration (FDA) or other government agencies, like prescription and over-the-counter drugs. This means that the consumer has the responsibility to ensure that a person buys a product that is safe, clean and effective. Simply reading the label may not provide enough information to make an informed purchasing decision for products like citrulline.

It is important to buy an organic product that is certified by an outside agency such as the United States Pharmacopeia, NSF International, or These organizations evaluate and report on the safety, purity, and efficacy of a product.

Other questions

How can I include citrulline in my daily diet?

Some of the best food sources of citrulline include:

  • Watermelon
  • Bitter gourd
  • Smash
  • Walnuts
  • Chickpea
  • Pumpkin
  • Cucumbers
  • Pumpkin

What type of cantaloupe is known to contain the highest levels of citrulline?

Studies have been done to evaluate different types of melon to find out which varieties offer the highest levels of citrulline. According to a study published in the Journal of Horticulturae , "watermelon is the most important natural plant source of L-citrulline, a non-protein amino acid that benefits the cardiovascular system and increases vasodilation in many tissues of the body."

Watermelon is a member of the gourd family, which includes squash, cantaloupe, squash, and cucumber.

Specific types of cantaloupe that according to the Journal of Horticulturae study have the highest citrulline content include:

  • Sweet raspberry watermelon
  • Watermelon Dixily
  • Kasaba type melon
  • Mouse melon
  • Horned melon rind
  • Bitter gourd
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