Does L-citrulline lower blood pressure and boost exercise performance?

Most people who want to raise nitric oxide try taking L-arginine directly — but this approach is limited by poor oral bioavailability. Arginase enzymes in the gut and liver break most of it down before it reaches circulation. L-citrulline sidesteps this problem entirely: it is absorbed intact through the small intestine, transported to the kidneys, and converted to arginine there. Reviews of the evidence conclude that citrulline supplementation raises arginine levels and nitric oxide synthesis more effectively than arginine supplementation itself⁶.

The resulting arginine fuels endothelial nitric oxide synthase (eNOS), the enzyme that produces nitric oxide in blood vessel walls. NO then diffuses into surrounding smooth muscle, triggering relaxation and vasodilation. This is the same pathway activated by exercise, sunlight, and dietary nitrates from beets and leafy greens — citrulline simply provides more substrate to keep it running. See our beets page for a complementary dietary route to NO support.

Erection is also a nitric oxide–mediated vascular event, so the same pathway matters for erectile function, but the evidence for citrulline's effect there is still preliminary.

Blood Pressure and Vascular Health

A 2019 systematic review and meta-analysis pooling 8 randomized controlled trials found that L-citrulline supplementation lowered systolic blood pressure by about 4 mmHg on average, and that diastolic pressure fell significantly only in the trials that used 6 g/day or more¹. The effect is most evident in people with prehypertension or hypertension, and not in people whose blood pressure is already normal⁷.

A 2022 randomized trial in hypertensive postmenopausal women tested 10 g/day of L-citrulline for 4 weeks². The researchers used brachial artery flow-mediated dilation — a validated imaging measure of endothelial function — alongside blood pressure monitoring. L-citrulline increased both plasma arginine and flow-mediated dilation, and reduced aortic diastolic blood pressure and mean arterial pressure compared to placebo. The findings are particularly relevant for women after menopause, when the loss of estrogen impairs eNOS activity and accelerates vascular aging.

Metabolic Health and Type 2 Diabetes

Citrulline also shows early promise for people with metabolic conditions⁶. In patients with type 2 diabetes, one month of 2,000 mg/day produced a 38% increase in plasma nitric oxide and a 21% reduction in arginase activity⁹. Arginase is an enzyme that competes with nitric oxide synthase for the same arginine, so when it is overactive — as it often is in diabetes — less arginine is available for NO production and blood vessel function suffers⁹. By reducing arginase activity, citrulline may help shift the balance back toward NO production and healthier vascular tone.

Exercise Performance

Much of the exercise research uses citrulline malate — L-citrulline bound to malic acid in a 2:1 ratio. The malate component may contribute independently by supporting the citric acid cycle, potentially improving energy production during sustained high-intensity effort.

The most-cited trial in this area tested 8 g of citrulline malate taken before a bench press protocol in 41 men³. Compared to placebo in a double-blind crossover design, citrulline malate increased the number of repetitions completed across 16 sets by more than 50%. Post-exercise muscle soreness was reduced by 40% at both 24 and 48 hours. Later meta-analyses confirmed a consistent, if more modest, ergogenic effect across different training contexts.

A 2020 meta-analysis of 13 trials found that citrulline supplementation reduced perceived effort during exercise (p = 0.03) and muscle soreness at 24 hours post-exercise (p = 0.04)⁴. Blood lactate levels were not significantly affected, suggesting the anti-fatigue effect works through mechanisms beyond simple lactate clearance — possibly including enhanced blood flow to working muscles and faster removal of metabolic waste.

Head to head, a 7-day crossover trial in 10 healthy men found that 6 g/day of L-citrulline improved oxygen-uptake kinetics and tolerance of severe-intensity cycling, while the same dose of L-arginine did not⁸.

Practical Dosage

For blood pressure support: 3–6 g L-citrulline per day, ideally taken consistently for at least 4–6 weeks.

For exercise performance: 6–8 g citrulline malate (2:1 form), or 4–6 g pure L-citrulline, taken 40–60 minutes before training.

Food sources: Watermelon is the richest dietary source — roughly 2–3 g of citrulline per kilogram of flesh, or about 1 g per two cups — and the white rind contains more citrulline than the red flesh. Cucumber, pumpkin, squash, and bitter melon also contain meaningful amounts, though supplemental doses far exceed what food provides: about 500 g of watermelon a day supplies only 1–1.5 g, compared with the 3–6 g a day used for blood pressure support.

L-citrulline is well tolerated with a low side effect profile. Mild gastrointestinal discomfort is occasionally reported at high doses (8+ g), and doses of up to 10 g/day have been used in short-term trials². No serious adverse events have been reported in human trials to date. People taking blood pressure medications or PDE5 inhibitors (e.g., sildenafil) should use caution, since the blood-pressure-lowering effects could add up.

Overview

Allerton et al. (2018) reviewed the case for L-citrulline in cardiometabolic health⁶. They note that oral arginine is largely ineffective at raising nitric oxide for a variety of reasons, whereas citrulline is not quantitatively extracted by the gut or liver and so is more effective at raising arginine levels and nitric oxide synthesis. They describe its blood-pressure-lowering effect as promising in adults with prehypertension or hypertension, with animal evidence for protection of the blood vessel lining, and the evidence for benefits to muscle and metabolic health, mainly in older or susceptible people, as preliminary. The review closes by identifying where further research is needed.

Blood Pressure and Endothelial Function

Barkhidarian et al. (2019) conducted a systematic review and meta-analysis of randomized controlled trials of L-citrulline and blood pressure; 8 trials, yielding 10 data sets, met the inclusion criteria¹. Sample sizes ranged from 12 to 34 participants, mean ages from 22 to 71 years, doses from 3 to 9 g/day, and durations from 1 to 17 weeks. Pooled across trials, supplementation lowered systolic blood pressure by 4.10 mmHg (95% CI −7.94 to −0.26; p = 0.037). The overall change in diastolic pressure (−2.08 mmHg; 95% CI −4.32 to 0.16; p = 0.069) did not reach significance, but a subgroup analysis found a significant diastolic reduction in the trials that used 6 g/day or more (−2.75 mmHg; 95% CI −5.37 to −0.12; p = 0.04). Sample sizes this small are reasonable for mechanistic vascular studies but not large enough to draw conclusions about hard clinical endpoints like cardiovascular events. A reduction of about 4 mmHg is modest for an individual but meaningful at the population level, where reductions of that size are associated with lower rates of stroke and coronary heart disease.

Maharaj et al. (2022) conducted a well-controlled crossover trial in 25 hypertensive postmenopausal women, testing 10 g/day L-citrulline versus placebo over 4 weeks per condition². The crossover design is valuable here because each participant serves as their own control, reducing confounding from the substantial individual variation in vascular function. Key outcomes included plasma L-arginine (confirming the citrulline-to-arginine conversion pathway was working as expected), brachial artery flow-mediated dilation measured by ultrasound (confirming improved endothelial function), and automated blood pressure measurement. Aortic diastolic BP and mean arterial pressure were significantly reduced with L-citrulline versus placebo. The authors attributed the effects to increased L-arginine availability driving eNOS activity. This trial is notable for using both mechanistic biomarkers and clinical outcomes simultaneously.

Figueroa et al. (2017) reviewed L-citrulline and watermelon together, treating both as sources of the same arginine–nitric oxide pathway⁷. Acute intake clearly raises plasma arginine, but the short-term gain in nitric oxide production and vasodilation is inconsistent, which the authors suggest is why a single dose of citrulline or watermelon has not reliably improved exercise tolerance. Chronic supplementation, by contrast, increased nitric oxide synthesis, lowered blood pressure, and may increase peripheral blood flow, changes that paralleled better skeletal muscle oxygenation and endurance performance. The blood-pressure-lowering effect was evident in adults with prehypertension or hypertension but not in people with normal blood pressure, although citrulline may blunt the blood pressure response to exercise in normotensive men.

Exercise Performance

Pérez-Guisado and Jakeman (2010) established the foundational evidence for citrulline malate in resistance training³. Their randomized, double-blind crossover study had 41 men complete two separate pectoral training sessions — one with 8 g citrulline malate and one with placebo, separated by a washout period. The increase in repetitions to failure exceeded 50% on citrulline malate versus placebo. The 40% reduction in muscle soreness at 24 and 48 hours post-exercise was equally striking. While these effect sizes are larger than what later meta-analyses found on average, the study was important for establishing the plausibility and direction of citrulline's ergogenic effect in a real training protocol.

Vårvik, Bjørnsen, and Gonzalez (2021) pooled data from 8 double-blind, placebo-controlled trials (137 participants, including 101 trained men, 26 women, and 9 untrained men) in a formal meta-analysis focused on repetition performance during strength training⁵. They found a statistically significant ergogenic effect of citrulline malate (Hedges's g = 0.20): 6–8 g taken 40–60 minutes before exercise increased repetitions by 3 ± 5 (6.4 ± 7.9%) compared with placebo (p = .022), a small advantage. The lower-body subanalysis showed a tendency toward an effect (SMD 0.27, p = .051), while the upper-body effect was not significant (SMD 0.16, p = .131). The authors concluded that acute citrulline malate supplementation may delay fatigue and enhance muscle endurance during high-intensity strength training.

Rhim et al. (2020) analyzed the recovery side of the equation, pooling 13 trials totaling 206 participants⁴. Their meta-analysis found significant reductions in perceived exertion (standardized mean difference, p = 0.03) and muscle soreness at 24 hours (p = 0.04). The 48-hour soreness result trended toward significance. Blood lactate at multiple post-exercise time points did not show significant reductions, which argues against the simple hypothesis that citrulline works by clearing lactate. The authors suggest enhanced blood flow, improved oxygen delivery, and potentially malate's role in the citric acid cycle as more likely contributors.

Bailey et al. (2015) compared citrulline with arginine directly⁸. In a randomized, placebo-controlled crossover study, 10 healthy men completed moderate- and severe-intensity cycling on days 6 and 7 of separate 7-day periods of placebo, L-arginine (6 g/day), and L-citrulline (6 g/day). Plasma arginine rose by a similar amount with both supplements, yet only citrulline lowered mean arterial pressure and improved exercise outcomes; arginine changed none of them. During severe-intensity cycling, citrulline shortened the oxygen-uptake mean response time from 59 ± 8 seconds with placebo to 53 ± 5 seconds, lengthened the time the men could sustain the effort (589 ± 101 versus 661 ± 107 seconds), and slightly increased the total work completed (123 ± 18 versus 125 ± 19 kJ). The study was small and enrolled only men.

Metabolic Health and Type 2 Diabetes

Shatanawi et al. (2020) gave 2,000 mg/day of L-citrulline for one month to 25 patients with type 2 diabetes⁹. Plasma nitric oxide rose by 38% and arginase activity fell by 21%. Arginase competes with nitric oxide synthase for arginine and is elevated in diabetes, so lowering it should leave more arginine available for nitric oxide production. Glycated hemoglobin (HbA1c) improved modestly, but not significantly. In cultured endothelial cells grown in high glucose, citrulline also prevented the rise in arginase activity and restored nitric oxide production. The study did not assess cardiovascular outcomes directly, but the changes in nitric oxide are consistent with better endothelial function, and vascular dysfunction is a major driver of illness and death in type 2 diabetes.

Limitations

The exercise literature is complicated by the common use of citrulline malate rather than pure L-citrulline, making it difficult to attribute effects to citrulline specifically versus the malate component. Most trials are acute (single dose) rather than chronic, and the long-term effect of daily citrulline supplementation on training adaptations has not been well studied. For blood pressure, the clinical trials are generally small and short-duration; the lack of long-term outcome data means that blood pressure reduction cannot yet be confidently linked to reduced cardiovascular event rates. Evidence is more preliminary still for metabolic health and erectile function. Nonetheless, the mechanistic plausibility — improving nitric oxide bioavailability — is well established, and the short-term evidence for both blood pressure and exercise outcomes is consistent enough to support L-citrulline as one of the better-evidenced amino acid supplements available.