Citrulline: Benefits, Dosage, and Potential Risks

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 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. Valerophenone

Citrulline: Benefits, Dosage, and Potential Risks

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.

Dietary supplements are not regulated like drugs in the United States, meaning the Food and Drug Administration (FDA) does not approve them for safety and effectiveness before products are marketed. When possible, choose a supplement tested by a trusted third party, such as USP, ConsumerLabs, or NSF. 

However, even if supplements are third-party tested, that doesn’t mean they are necessarily safe for all or effective in general. Therefore, it is important to talk to your healthcare provider about any supplements you plan to take and check in about potential interactions with other supplements or medications.

Citrulline is naturally produced in the body, even if you do not consume it. Upon ingestion, citrulline breaks down into l-arginine and stimulates the production of the natural compound nitric oxide.

By itself, nitric oxide supplementation is known to improve cardiac health, enhance exercise performance, reduce high blood pressure during pregnancy, reduce erectile dysfunction (ED), and improve healing and respiration.

L-arginine is supposed to be a therapeutic agent for improving immune function and lowering blood pressure. There is also evidence that it helps regulate metabolism and alleviate symptoms of type II diabetes.

In theory, taking citrulline supplements can help your body produce more of these essential compounds, ushering in the benefits they each have to offer. Here's what researchers know about the benefits of citrulline so far:

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.

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 in athletes.

The National Institutes of Health (NIH) states that current research does not offer strong enough evidence for taking citrulline or citrulline malate supplements for exercise or athletic performance.

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.

Citrulline may reduce blood pressure, but more research is needed. Citrulline is converted to arginine in the body, and arginine increases blood flow. Therefore, it is theorized that citrulline could help with blood pressure control. Studies have shown that short-term L-citrulline use can lower blood pressure in adults with hypertension (high blood pressure) and those with pre-hypertension. These studies suggest that pharmaceutical-grade L-citrulline helped promote heart health. A systematic review and meta-analysis found that L-citrulline supplementation may reduce systolic and possibly diastolic blood pressure, but only in studies that used doses greater than or equal to 6 grams/day. Yet another review and meta-analysis found no beneficial effect of citrulline on blood pressure. Your best bet for managing high blood pressure is to discuss a care plan with your healthcare provider that includes evidence-based practices for hypertension, like the DASH diet, weight management, and blood pressure medications. Always discuss any supplements you take with your healthcare provider.

An erection is largely brought on by the actions of nitric oxide. In fact, some drugs used to treat erectile dysfunction, such as phosphodiesterase type-5 inhibitors, work by enhancing nitric oxide production.

According to a 2017 study of people with erectile dysfunction, levels of citrulline and l-arginine were lowest in people with severe ED compared to those with mild ED. The researchers concluded that increasing these two compounds could relieve erectile dysfunction by helping the body produce more nitric oxide.

Few studies have specifically examined the effects of citrulline supplementation on erectile dysfunction. In one study, citrulline supplementation led to significant improvements in erection stability and firmness, as well as intercourse satisfaction in men with ED. However, citrulline supplements were taken in combination with the natural phenol transresveratrol.

Larger, long-term studies focused on citrulline alone are needed to further investigate its potential for treating ED.

The body converts citrulline into l-arginine then nitric oxide, two compounds that help stimulate testosterone production. It's thought that citrulline supplementation could help build testosterone for this reason. However, more specific studies in humans are needed to prove any link.

Citrulline is a non-essential amino acid, meaning that your body produces it on its own. Once ingested, the body converts citrulline into arginine in the kidneys. Afterward, arginine converts into nitric oxide, which dilates blood vessels and improves circulation. Excess citrulline is eventually broken down by the liver.

Dietary supplements containing citrulline can be found in two formulations:

One gram of citrulline malate provides 566 mg of citrulline, compared to one gram (1000 mg) of pure citrulline. Malic acid is an organic compound that gives many fruits their tart taste. It is combined with citrulline to help your body absorb it better.

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:

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

The best source of citrulline is watermelon. One cup of watermelon contains 365 mg of citrulline. Other sources of citrulline include:

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:

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.

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.

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

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:

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

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.

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Shirai M, Hiramatsu I, Aoki Y, Shimoyama H, et al. Oral l-citrulline and transresveratrol supplementation improves erectile function in men with phosphodiesterase 5 inhibitors: a randomized, double-blind, placebo-controlled crossover pilot study. Sex Med. 2018;6(4):291-296. doi:10.1016/j.esxm.2018.07.001

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By Jennifer Lefton, MS, RD/N, CNSC, FAND Jennifer Lefton, MS, RD/N-AP, CNSC, FAND is a Registered Dietitian/Nutritionist and writer with over 20 years of experience in clinical nutrition. Her experience ranges from counseling cardiac rehabilitation clients to managing the nutrition needs of complex surgical patients.

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Citrulline: Benefits, Dosage, and Potential Risks

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