What Is Citrulline?

Have you heard of citrulline? It’s an amino acid that you produce naturally. But it’s also in some foods, like watermelon, as well as sold in supplement form.

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There’s a lot of hype about this supplement, especially in the fitness world, says registered dietitian Devon Peart, RD, MHSc.

“Citrulline is trendy among bodybuilders and athletes because even a small improvement in performance — even if it’s a placebo — could give them a competitive advantage.”

But what does the research say about citrulline? Is it a safe performance booster? A waste of money? A dangerous supplement? Peart explains what you need to know if you’re thinking about taking a citrulline supplement.

How does citrulline work?

Citrulline is involved in your urea cycle, which gets rid of waste products by excreting them in urine (pee). It’s converted into arginine, an amino acid that produces nitric oxide, a substance that relaxes blood vessels and improves blood flow.

“The main mechanism by which citrulline could be beneficial for muscle is by increasing nitric oxide, leading to increased blood flow,” says Peart.

The types of citrulline

There are two main forms of citrulline.

L-citrulline

The form naturally found in your body, in some foods and in supplements is L-citrulline.

There’s some research-based evidence that L-citrulline may be helpful for athletic performance because it improves blood flow to working muscles.

The potential benefit seems to apply more to anaerobic exercise such as strength training, rather than aerobic exercise, like running. Still, future research might offer more clarity.

One study of avid cyclers found that the group taking L-citrulline biked faster and felt less tired after cycling 4 kilometers (roughly 2.5 miles). Participants took 2.4 grams of the supplement every day for eight days before the bike ride.

Citrulline malate

Citrulline malate is also receiving some attention lately. This form is a combination of citrulline with malic acid. Malic acid is found in apples, among other fruits.

Citrulline malate is a direct precursor to nitric oxide. It’s thought that this form of citrulline could have bigger effects because it potentially increases ATP — adenosine triphosphate, or the fuel for working muscles — production and availability.

There’s some research that citrulline malate may be beneficial for muscular endurance and strength performance. But overall evidence is mixed on its effectiveness, and more research is needed.

“In the meantime, since there is a good level of evidence for L-citrulline, I recommend using that form of the supplement until there is more evidence for the use of citrulline malate,” Peart says.

Three possible benefits of taking L-citrulline

If you’re looking to take citrulline in supplement form, Peart recommends taking L-citrulline rather than citrulline malate.

“There’s more evidence of L-citrulline’s benefits,” she notes. “And there’s less research on citrulline malate. The research that does exist is conflicting.”

People take L-citrulline supplements to improve blood flow, which may:

1. Give you a more effective workout

Taking L-citrulline may benefit your workout by boosting your endurance. One study looked at how L-citrulline supplements could affect athletic performance. Researchers found that when participants took 6 grams of L-citrulline for seven days, they could work harder for longer on a severe-intensity exercise test.

But a recent overview of existing research on L-citrulline and aerobic exercise came to a different conclusion. According to the review, there isn’t a clear answer to whether taking L-citrulline can help you gain a competitive edge. Some studies suggested a benefit to taking the supplement, while others showed it doesn’t make a difference.

“The average gym-goer may notice a benefit during their workout, in terms of performance,” notes Peart. “And for avid athletes who may work out multiple times a day, L-citrulline could increase your performance and help you recover faster.”

2. Reduce high blood pressure

If you have high blood pressure, taking a citrulline supplement could help. An analysis of research on citrulline’s effect on blood pressure found positive outcomes in most studies.

Study participants took from 3 to 8 grams of L-citrulline a day. Researchers analyzed results anywhere from one to 16 weeks after use.

According to the analysis, citrulline seemed like it could significantly lower blood pressure. But researchers recommended larger clinical trials to not only confirm promising findings, but also to determine ideal dose amounts and if there were any side effects.

3. Help with erectile dysfunction

Have you thought about trying aphrodisiacs to spice up your sex life? Eating oysters and chocolate (in moderation) won’t hurt you. But if you’re using an aphrodisiac because of erectile dysfunction (ED), it probably won’t do much.

But some people believe citrulline is useful for ED. They theorize that because limited blood flow is one of the causes of ED — and because citrulline improves circulation — it could help.

“It’s been suggested as a possibility,” states Peart. “But the jury’s still out on that.”

In one small but promising study, 50% of the participants had positive effects. They took 1.5 grams of L-citrulline a day for a month. Twelve out of 24 people went from having mild ED to typical erectile function. Scientists recommended further research and studies in this area.

Citrulline dosage

If you want to try a L-citrulline supplement, see a healthcare provider first. Supplements themselves aren’t well-regulated in the U.S., and their side effects aren’t well-documented. Plus, some supplements can interact badly with other medicines you might be taking.

If you’re cleared to take L-citrulline, a safe dosage is 3 to 6 grams a day. Start with the lowest amount. You can always increase the dosage to see if it affects your results if you don’t experience any side effects.

Does citrulline have any side effects?

Amino acids like citrulline can cause gastrointestinal upset. That’s why it’s important to start at the smallest dose to see how your body reacts. Side effects may include:

• Bloating.
• Cramping.
• Diarrhea.
• Sweating.

Foods that contain L-citrulline

L-citrulline is particularly abundant in watermelon. You can also boost your level of nitric oxide — a component that increases blood flow — with foods high in nitrates, including:

Scientists don’t yet agree on the benefits of citrulline, and research provides mixed results on its scientific benefits. Want a guaranteed home run? Adopting a heart-healthy lifestyle — a nutritious diet, regular exercise and no smoking — is a proven way to help you win at living your best life.

Citrulline Malate & L-Citrulline Guide: Benefits, Dosages & FAQ

This complete guide explores the benefits and dosages of L-citrulline supplements. Learn about citrulline and citrulline malate and how they can help you reach your goals.

This Guide Teaches You:

• About the physiological role and benefits of citrulline.
• Who should consider taking a citrulline supplement.
• When to take citrulline malate, and what the recommended dosage is.

Table of Contents:

1. 1. Introduction
2. 2. Physiological role of citrulline
3. 3. Primary benefits of citrulline (malate) supplementation
4. 4. Possible side effects of citrulline supplementation
5. 5. Who should or should not use citrulline
6. 6. When to take citrulline
7. 7. Recommended dosing
8. 8. Citrulline Malate FAQs

Citrulline is a nonessential alpha-amino acid that is not coded for by human DNA but is still present in certain proteins and the urea cycle (either as a by-product of arginine oxidation or from reaction of carbamoyl phosphate and ornithine). Citrulline appears to have a variety of synergistic effects with other popular peri-workout supplements, such as branched-chain amino acids (BCAAs).

It is naturally produced in the rind and flesh of watermelon and is gaining ground as a useful ingredient in the field of dietary/sports supplements.

Physiological role of citrulline

Citrulline plays a variety of physiological roles, but is primarily relegated to augmentation of nitric oxide-dependent signaling. (1) Citrulline is manufactured by a variety of other amino acids in the liver and is an important component of the urea cycle; the urea cycle facilitates the elimination of ammonia and other nitrogenous toxins from the blood (most of which takes place in the liver of mammals). Nitrogen metabolites accrue from digestion, absorption, and metabolism of proteins.

Oral citrulline supplementation has been shown to increase increase plasma arginine concentration and thus enhances production of arginine-derived metabolites (i.e. nitrite, ornithine, creatinine, etc). (2) As aforementioned, this is crucial as synthesis and elimination of urea is necessary for removing toxic nitrogen metabolites from the body. Citrulline works along with citric acid, aspartic acid, and magnesium to improve nitrogen metabolite excretion.

A rare disorder in humans called citrullinemia may cause buildup of ammonia in the blood; this occurs when there is a deficiency of the enzyme necessary to catalyze the [citrulline-arginine] reaction of the urea cycle. Research seems to indicate that zinc supplementation can improve the conversion of citrulline to arginine in the liver and lower blood ammonia levels. (3)

Moreover, since pyridoxine (vitamin B-6) activates transaminases (i.e. enzymes that convert an amino acid to a different amino acid) in the urea cycle, it may be useful to supplement with if there is a suspected malfunction in the liver. As always though, these clinical abnormalities should be addressed by your personal care physician.

Primary benefits of citrulline (malate) supplementation

Citrulline supplementation, generally in malic acid salt form, has been garnering attention in the realm of physical performance enhancement and its benefits are numerous. Aside from being a necessary biomolecule in the urea cycle, citrulline may enhance health and performance by:

• Increasing intracellular NO production which is a positive regulator of vasodilation and blood flow (2)
• Enhancing the utilization of essential amino acids during exercise (1)
• Improving recovery time after exercise by attenuating delayed-onset muscle soreness (4)
• Enhancing elimination of toxic nitrogen metabolites (2)
• Increasing growth hormone levels to a higher degree in individuals after resistance training as compared to a placebo group (1)
• Reducing/inhibiting the increase in plasma insulin levels that usually arises after high-intensity exercise (3)

Possible side effects of citrulline supplementation

Thankfully, citrulline is a rather safe compound and the side effects are limited and generally benign. The most prevalent side effect for people supplementing with citrulline tends to be gastrointestinal distress, but this can be ameliorated by taking citrulline on an empty stomach.

Who should or should not use citrulline:

• Physique competitors
• Athletes involved in aerobic and/or anaerobic events/sports
• Powerlifters
• Those looking for increased blood flow and “pumps” during training
• Avoid use if you have citrullinemia as this would only compound the issue

When to take citrulline:

• Optimally, citrulline should be ingested about 15-30 minutes before training.
• May also take citrulline during and/or after training if desired

Recommended dosing:

• Start with a once-daily dose of 6-7g
• If desired, dose may be increased to 15-20g split into multiple doses throughout the day

Citrulline Malate FAQs:

Q: Can I just eat watermelon rather than supplementing with citrulline?

A: Most of the citrulline content in watermelons is found in the rind of the fruit, therefore it is not very practical to obtain the doses of citrulline suggested herein through diet.

Q: Is it true citrulline may enhance libido and treat impotence?

A: This is actually another nice “benefit” of citrulline supplementation as the increase in nitric oxide will relax blood vessels and increase blood flow (which can help improve erections, among other things).

Q: I’ve heard citrulline should be taken on an empty stomach, is this true?

A: This is likely due to the rare occurrence of stomach distress that may occur after ingesting citrulline; it is fine to take citrulline at meal times if you tolerate it well.

Q: How long does it usually take for me to notice the effects of citrulline?

A: This will vary for most individuals, but acute effects such as endotoxin removal will happen after the first dose; more latent benefits such as strength increases and decreased DOMS may take a few weeks to notice.

References:

1) Sureda A, Córdova A, Ferrer MD, Pérez G, Tur JA, Pons A. L-citrulline-malate influence over branched chain amino acid utilization during exercise. Eur J Appl Physiol. 2010 Sep;110(2):341-51. doi: 10.1007/s00421-010-1509-4. Epub 2010 May 25. PubMed PMID: 20499249.

2) Wijnands KA, Vink H, Briedé JJ, van Faassen EE, Lamers WH, Buurman WA, Poeze M. Citrulline a more suitable substrate than arginine to restore NO production and the microcirculation during endotoxemia. PLoS One. 2012;7(5):e37439. doi: 10.1371/journal.pone.0037439. Epub 2012 May 29. PubMed PMID: 22666356; PubMed Central PMCID: PMC3362574.

3) Marchesini, G., Fabbri, A., Bianchi, G., Brizi, M., & Zoli, M. (1996). Zinc supplementation and amino acid‐nitrogen metabolism in patients with advanced cirrhosis. Hepatology, 23(5), 1084-1092.

4) Pérez-Guisado, J., & Jakeman, P. M. (2010). Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. The Journal of Strength & Conditioning Research, 24(5), 1215-1222.

5) Hickner RC, Tanner CJ, Evans CA, Clark PD, Haddock A, Fortune C, Geddis H, Waugh W, McCammon M. L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc. 2006 Apr;38(4):660-6. PubMed PMID: 16679980.