L-Citrulline Benefits: What Human Studies Show, Doses, Safety

L-citrulline is an amino acid your body makes on its own and that is also found in watermelon. Human studies point to a modest drop in blood pressure in middle-aged and older adults, a small and uncertain effect on exercise, and one small trial in mild erectile dysfunction. Many other claims, such as benefits for kidneys, gut, brain or muscle building, rest mostly on animal and cell studies.

Quick facts

What do human studies show about L-citrulline benefits?

Blood pressure and artery health

This is the best-supported use. A 2025 meta-analysis of 15 randomized trials (415 participants, middle-aged and older adults) pooled L-citrulline and watermelon studies. Systolic pressure (the top number) fell by about 4.0 mmHg and diastolic by about 2.5 mmHg. A subgroup that used citrulline together with L-arginine fell more, by about 10 mmHg systolic. That subgroup mixes two ingredients, so it does not show what citrulline does alone.

A 2026 systematic review of 12 trials in 360 postmenopausal women (4 to 8 weeks, all in the United States) found most blood pressure studies showed lower systolic pressure, with reductions up to 9 mmHg in some studies in women with high blood pressure. Results for artery stiffness and blood vessel function were mixed, and there was no consistent effect on weight, glucose, insulin or blood fats. The authors said larger trials are needed before clinical recommendations.

One caution: a lower blood pressure number is a stand-in for health outcomes like heart attack or stroke. Our guide to surrogate outcomes in trials explains why that gap matters. The trials here measured the number, not heart disease. A 2018 review in Nutrients also notes that effects on resting central blood pressure were less consistent than effects under stress such as cold exposure, and that population, dose and duration changed the size of the effect.

A smaller trial summarized by a clinician-run site, Dr Stanfield, tested 5 g of L-citrulline morning and night for 4 weeks in 25 postmenopausal women with high blood pressure. Blood vessel dilation improved, but blood pressure did not change significantly.

Exercise performance

A 2026 systematic review and meta-analysis of citrulline malate pooled 30 randomized trials (644 participants). It found a small improvement in overall performance (effect size 0.16), but the range of plausible results was wide and the certainty of the evidence was rated low to very low. Perceived exertion did not change significantly. Differences by sex, training status, dose and timing were not significant, and the authors said reliable dosing, timing and target groups have not been established.

Single doses before a workout have mostly done little. Dr Stanfield’s summary describes several small trials of one pre-exercise dose that found no benefit, and one that found more muscle soreness. Multi-day use looked better in a small study of 10 recreationally active men who took 6 g a day for seven days: it improved exercise tolerance by 12% in a severe-intensity cycling test, while L-arginine at the same dose did not. Cleveland Clinic describes a cycling study (2.4 g a day for eight days) with faster 4 km times, and notes a recent overview in which some studies found a benefit and others did not.

Mild erectile dysfunction

The evidence is one small trial. As described by Cleveland Clinic, 24 men took 1.5 g of L-citrulline a day for a month, and 12 moved from mild erectile dysfunction to typical erectile function. WebMD calls it a small study. Dr Stanfield’s summary adds that only 2 men improved on placebo, that no adverse events were reported, and that the researchers noted L-citrulline is less effective than prescription medicine. Cleveland Clinic’s dietitian says "the jury’s still out" on citrulline for this use. No trial has compared it head to head with sildenafil (Viagra) or tadalafil (Cialis).

Body composition

A 2025 meta-analysis of 21 trials found no overall effect of citrulline or watermelon on BMI, weight, fat mass, waist size or fat-free mass. Some subgroups (over 40 years old, more than 6 g a day, 3 to 8 weeks for fat-free mass) looked better, but the authors call these exploratory.

Everything else: preliminary or animal-based

• Muscle building: a 2025 review in Nutrients says most evidence is from animal and cell studies, human trials are limited and inconsistent, and the effect is less potent than leucine or branched-chain amino acids.
• Heart failure: two small studies described in the 2018 review suggested better heart function, but they were small, and the Dr Stanfield summary notes one had no placebo group.
• Fatty liver: in a trial of 42 adolescents, 6 g a day did not reduce liver fat versus placebo (per Dr Stanfield).
• Pre-eclampsia: a 2025 review found only one citrulline study (36 women), with no effect on pre-eclampsia or blood pressure. The promising results in that review were for L-arginine.
• Depression, sickle cell disease, gut immunity: WebMD says the research on these is thin; the Nutrients review says gut and immune findings are largely from animals.

For how to weigh reviews like these, see our guide to meta-analyses and systematic reviews.

Is there a benefit to taking it daily, and for whom?

Men: the only male-specific use studied is mild erectile dysfunction (one small trial). Exercise reviews found no significant difference by sex.

Women: the main human data are in postmenopausal women, where blood pressure results were the most consistent and muscle benefits appeared only when citrulline was combined with resistance training. Data in pregnancy are very thin (see above), and WebMD says there is not enough research on pregnancy or breastfeeding.

Kidneys: the kidneys convert citrulline into arginine, which is why they appear in the biology. No human trial described here shows that citrulline protects kidneys. Dr Stanfield’s summary advises caution in severe kidney disease because data are limited.

L-citrulline vs L-arginine: which works better?

Your body turns citrulline into arginine, and arginine is the raw material for nitric oxide, which relaxes blood vessels. The 2018 review explains that much oral arginine is broken down in the gut and liver, while citrulline mostly passes through. In one study cited there, 0.75 g of citrulline twice a day raised arginine levels about as much as 1.6 g of arginine twice a day. Large arginine doses (around 13 g) can upset the stomach, and citrulline caused less distress in that review. Whether this edge means better health results is less clear: citrulline trials are small, and the strongest blood pressure subgroup used both together.

Can L-citrulline replace Viagra or Cialis, and is anything 10 times stronger?

No. The one small trial found some improvement in mild erectile dysfunction, and the researchers noted it is less effective than prescription medicine. No head-to-head trial exists, so nothing in the research supports a claim that citrulline, or anything else sold as a supplement, is stronger than these drugs. If erectile dysfunction is the problem, a clinician can sort out causes and options, and nothing here is a reason to change a prescribed medicine.

Doses used in studies

These are amounts researchers gave participants, not advice.

The 2018 review summarized the working range as roughly 3 g to 10 g a day. Cleveland Clinic and WebMD both describe 3 to 6 g a day as typical. The 2026 exercise review says reliable dosing and timing have not been established. Getting 3 g from fresh watermelon would take about 1 to 1.5 kg a day, according to the 2018 review.

How long does it take to work, and can you have coffee with it?

Blood levels move fast. Citrulline peaks within about an hour of a dose (2025 review), arginine peaks around 1 to 2 hours, and citrulline returns to baseline within about 8 hours (2018 review). Feeling or measuring a benefit is slower. Blood pressure trials ran for weeks, the erectile dysfunction trial for a month, and healthy young people given a single dose or about a week did not show improved artery dilation. Coffee was not tested in the studies above. If you take blood pressure medicine, a pharmacist can tell you whether anything you drink matters.

Side effects, downsides and liver safety

Is it hard on the liver? The 2018 review says oral citrulline is not taken up by the liver the way arginine is, and mostly bypasses it. No human trial reported here found liver harm. The review does mention one rat study in which early-life supplementation was linked to blood fat patterns that could lead to liver disease, and it says more safety work is needed at all life stages. That is animal data, not proof of harm in people.

What not to mix with L-citrulline

WebMD says citrulline may cause blood pressure to drop too low if you take PDE5 inhibitors for erectile dysfunction, blood pressure medicines, or nitrate medicines for heart conditions. Dr Stanfield’s summary lists the same classes and notes one trial combining citrulline with a PDE5 inhibitor reported no adverse events, but advises caution anyway. The same summary reports no established bleeding risk and no significant alcohol interaction. Check with a pharmacist before combining any of these with a supplement.

Who should talk to a clinician first

• Anyone taking blood pressure medicine, nitrates, or erectile dysfunction medicine
• People with low blood pressure, heart failure, pulmonary arterial hypertension, or severe kidney disease
• People with a urea cycle disorder (Dr Stanfield’s summary says citrulline could affect tests used to monitor these)
• Anyone pregnant or breastfeeding
• Anyone with surgery scheduled (some sources suggest a clinician may advise stopping supplements beforehand)

Cleveland Clinic also notes that supplements are not well regulated in the U.S. and some interact badly with medicines, and it advises seeing a healthcare provider first.

What is still unknown

• Whether blood pressure drops from citrulline lead to fewer heart attacks or strokes
• The best dose, timing and form for any use, since exercise reviews report no reliable dosing
• Whether citrulline beats watermelon or arginine in head-to-head human trials
• How it compares with prescription erectile dysfunction drugs
• Long-term safety, and effects in pregnancy and in children
• Whether benefits in animals for gut, brain, liver and kidneys occur in people

How to read a label that lists L-citrulline

• Check the form. "L-citrulline" should be citrulline itself. "Citrulline malate" is only about 56.6% citrulline by weight per Dr Stanfield’s summary, so an 8 g serving gives roughly 4.5 g of citrulline.
• Look for the amount of citrulline, not just the compound. Study doses above are citrulline amounts, so a label’s total weight may overstate what you get.
• Be wary of "2:1" labels. The ratio is ambiguous, and independent testing of five "2:1" products in England found 52% to 66% citrulline, less than expected.
• Proprietary blends: if the label gives only a total for a blend, you cannot tell how much citrulline is in it. Ask the seller for the per-ingredient amount.
• Don’t rank products by claims. Our guide to ingredient evidence vs. marketing claims explains how to compare a label with the studies.

Before you order

• Ask the seller for the grams of citrulline per serving and whether it is free citrulline or malate.
• Ask whether the product has independent testing for its stated content.
• Tell your pharmacist or doctor about any blood pressure, nitrate or erectile dysfunction medicine.
• Decide which outcome you want, since the evidence is much stronger for blood pressure than for performance or sexual function.

By ClinicalStudyConnect.com Research Desk

This article is for general information purposes only and does not constitute medical advice. Consult your doctor or qualified healthcare provider before making changes to your health routine.