What Is Citrulline?

Citrulline, or l-citrulline, is a non-essential amino acid made in the liver and intestine. Some individuals take it as a dietary supplement. It can also be found in foods like watermelon.

Citrulline is an important amino acid for the urea cycle, which helps your body to get rid of harmful substances like ammonia. In the body, L-citrulline is transformed into a different amino acid called L-arginine. This is converted into a chemical called nitric oxide. The nitric oxide then acts as a vasodilator, widening the blood vessels. Citrulline is also said to have an antioxidant effect.

Citrulline is promoted to improve athletic performance and enhance heart health, but the research is limited. This article reviews citrulline's uses, side effects, dosage, and more about the supplement.

Uses of Citrulline

Supplement use should be individualized and vetted by a healthcare professional, such as a registered dietitian, pharmacist, or healthcare provider. No supplement is intended to treat, cure, or prevent disease. 

Most research on citrulline supplementation has examined its effects on physical and athletic performance. However, very little scientific evidence supports its use for this purpose.

Recent systematic reviews have shown mixed results.

A meta-analysis of eight studies suggested that supplementing with 6 to 8 grams of citrulline malate (a type of citrulline supplement) 40 to 60 minutes before exercise increased repetitions with lower body resistance exercises compared with the placebo.

However, in another meta-analysis, citrulline malate supplementation did not improve muscle strength in healthy, resistance-trained adults. This systematic review included four studies and 138 assessments.

A recent review of available research on citrulline concluded that insufficient evidence supports the claim that citrulline supplementation improves exercise performance by increasing blood flow. More well-controlled studies are needed.

In short, citrulline may potentially help with certain aspects of physical performance, but the results are too inconsistent to make any recommendations for supplementation for athletes.

What Are the Side Effects of Citrulline?

Citrulline has been used as an oral (by mouth) supplement for many years without reports of serious safety concerns.

Although citrulline side effects are uncommon, mild symptoms may include:

• Nausea
• Diarrhea

Precautions

Similar to most supplements, there is not enough data on the safety of citrulline in pregnant or breastfeeding people. For this reason, it's best to avoid taking citrulline supplements if you are pregnant or breastfeeding.

Always consult your healthcare provider before starting any new supplements to be safe.

Dosage: How Much Citrulline Should I Take?

Always speak with a healthcare provider before taking a supplement to ensure that the supplement and dosage are appropriate for your individual needs. 

There is no standard recommended dose for citrulline. Studies have used either citrulline or citrulline malate in differing amounts.

In studies, 2 to 5 grams of L-citrulline per day has been used for exercise performance enhancement. Studies have shown that doses of 3 to 6 grams per day of L-citrulline and 8 grams of citrulline malate can be taken with no side effects.

One study discovered that taking up to 15 grams of citrulline was safe and well-tolerated by the study participants.

Overall, using up to 9 grams for one day or 6 grams/per day for up to 16 days caused few safety concerns.

What Happens If I Take Too Much Citrulline?

There is little information available about what could happen if you take too much citrulline.

Generally, it is best to follow the instructions on the product label or ask your healthcare provider how much you should take. Immediately contact a healthcare provider if you start to experience any adverse reactions after taking citrulline.

Interactions

Supplements may have interactions with prescribed medications. Before starting citrulline, tell your healthcare provider or pharmacist about any other medicines you take or plan to take, including over-the-counter (OTC) nonprescription products, vitamins, herbs, supplements, and plant-based medicines.

The following drugs may interact with citrulline supplements:

• Phosphodiesterase-5 (PDE-5) inhibitors: PDE-5 inhibitors include drugs for erectile dysfunction, such as Viagra (sildenafil). It is suspected that combining citrulline with PDE-5 inhibitors may increase the effects of vasodilation and lowering blood pressure.
• Antihypertensive (blood pressure lowering) drugs: High blood pressure drugs include Norvasc (amlodipine), Cardizem (diltiazem), and Verelan (verapamil), among others. Because L-citrulline is also thought to have antihypertensive effects, combining it with antihypertensive therapies could theoretically increase the risk of severely low blood pressure. However, studies evaluating citrulline's effects on blood pressure have produced mixed results.

Other prescription medications could interact with citrulline. Always discuss your supplement use with a healthcare provider.

How to Store Citrulline

Always store supplements according to the manufacturers' suggestions. Keep them out of reach of children and pets to prevent accidental consumption.

Sources of Citrulline and What to Look For

Citrulline is found in several foods, but watermelon is the most potent source.

Citrulline is also available in supplement form as citrulline or citrulline malate. Understanding the difference between citrulline malate and citrulline supplements can help you decide which one you prefer:

• L-citrulline is citrulline without any other substance.
• Citrulline malate is made up of L-citrulline and DL-malate and is 56.64% citrulline by weight.

Citrulline is also added to supplement powders marketed for workouts and weight lifting, which contain many different ingredients. Some products contain creatine or caffeine and large amounts of specific vitamins and minerals.

Dietary supplements, such as citrulline, are not as strictly regulated by the Food and Drug Administration (FDA) as conventional drugs or foods. It’s important to purchase a product that has been certified by a third-party agency, such as:

• The U.S. Pharmacopeia
• NSF International
• ConsumerLab.com

These organizations evaluate and report on a product’s safety, purity, and potency level.

Summary

Citrulline is a non-essential amino acid. The body produces citrulline on its own, but it can also be found in foods, like watermelon, and supplement forms.

There has been a lot of interest in citrulline supplementation for improved athletic performance. Despite this, the evidence does not support its routine use for athletes. Currently, there are no standard recommendations for the use of citrulline supplements.