Can a healthy adult runner safely use L‑citrulline to modestly improve endurance and reduce muscle fatigue, and what dosage is recommended while considering contraindications such as renal impairment or hypotension?

L-Citrulline for Runners

Direct Answer

L-citrulline supplementation does not reliably improve endurance performance in healthy runners and should not be routinely recommended as an ergogenic aid. The most recent and highest-quality evidence shows no significant benefit for time-to-exhaustion or time-to-completion in endurance exercise, despite theoretical mechanisms involving nitric oxide production 1, 2.

Evidence Quality and Findings

Recent Systematic Review and Meta-Analysis

• A 2023 systematic review and meta-analysis of 9 randomized controlled trials (n=158 participants) found no significant difference in endurance performance after acute L-citrulline supplementation 1
• Time-to-exhaustion showed a pooled standardized mean difference of 0.03 (95% CI: -0.27 to 0.33), indicating no meaningful effect 1
• Time-to-completion showed a pooled standardized mean difference of -0.07 (95% CI: -0.50 to 0.15), also indicating no benefit 1
• Between-study heterogeneity was low (I² = 0%), strengthening confidence in these null findings 1

Most Recent High-Quality Trial

• A 2025 double-blind, randomized, placebo-controlled crossover trial using 10 days of continuous supplementation at 100 mg/kg/day (higher dose and longer duration than most prior studies) found no improvement in time-to-exhaustion at intensity above the second lactate threshold 2
• No significant differences were observed in cardiac output, oxygen uptake, blood pressure, or metabolic parameters between L-citrulline and placebo 2
• A trend toward benefit was noted in the female subgroup (p=0.06), but this did not reach statistical significance 2

Contradictory Older Evidence

• One 2016 study (n=22) reported a modest 1.5% improvement in 4-km cycling time trial performance after 7 days of 2.4 g/day L-citrulline supplementation 3
• However, this single positive study is outweighed by the more recent systematic review and larger body of null findings 1, 2

Dosing Protocols (If Considering Use Despite Limited Evidence)

Acute Dosing

• Single doses of 8 grams taken 1 hour before exercise have been the most commonly studied acute protocol 4, 5
• This acute approach has produced equivocal results and is not reliably effective 5

Continuous Dosing

• 2.4 to 8 grams per day for 7-10 days represents the range studied in continuous supplementation protocols 2, 3
• A relative dosing strategy of 100 mg/kg/day has been tested but showed no benefit 2
• The optimal dose remains undetermined due to inconsistent findings across studies 5

Safety Considerations and Contraindications

Renal Impairment

• L-citrulline should be avoided in patients with severe renal impairment (eGFR <30 mL/min), as it is metabolized to L-arginine and may accumulate 6
• Patients on dialysis have low serum carnitine (not citrulline, but related amino acid metabolism), and amino acid supplementation requires careful monitoring in chronic kidney disease 6
• Plasma citrulline levels are used as a marker of intestinal function and can be affected by renal dysfunction 6

Hypotension Risk

• L-arginine (the downstream product of L-citrulline metabolism) has been shown to modestly decrease systemic arterial pressure (92±4 to 87±3 mmHg) in patients with pulmonary arterial hypertension 6
• Runners with baseline hypotension or those taking antihypertensive medications should use caution, as nitric oxide-mediated vasodilation could exacerbate low blood pressure 6
• However, one study in normotensive volunteers showed no significant effect on blood pressure 6

General Safety Profile

• Short-term L-citrulline supplementation appears generally well-tolerated in healthy adults without significant adverse effects reported in trials 1, 2, 3
• No serious safety concerns have emerged in the sports nutrition literature for healthy individuals 5

Alternative Evidence-Based Strategies for Runners

Carbohydrate Strategies

• 30-60 grams of carbohydrates during endurance events lasting longer than 1 hour is strongly recommended by the American College of Sports Medicine 7
• Carbohydrate loading in the days before an event improves performance in exercises lasting longer than 1.5 hours 7
• Hypertonic fluids with carbohydrates and sodium improve water absorption efficiency during exercise 7

Hydration

• Maintain fluid balance during exercise, aiming to lose no more than 2-3% of body weight 7

Beta-Alanine (Alternative Supplement)

• Beta-alanine has more robust (though still contradictory) evidence than L-citrulline for improving muscle endurance through buffering acid buildup 7
• Recommended dosage is approximately 65 mg/kg body weight daily (up to 6.4 g/day) via split-dose regimen for 4-12 weeks 7
• However, evidence remains less robust than for caffeine and creatine 7

Common Pitfalls to Avoid

• Do not expect meaningful performance gains from L-citrulline supplementation based on current evidence, despite marketing claims about nitric oxide enhancement 1, 2
• Avoid using L-citrulline as a substitute for proven strategies such as proper carbohydrate intake, hydration, and structured training 7
• Be aware of supplement contamination risks: 15-25% of sports supplements may contain undeclared prohibited substances 7
• Choose products that have undergone third-party testing (e.g., NSF Certified for Sport, Informed-Sport) to minimize contamination risk 7
• Do not use in patients with significant renal impairment without medical supervision 6

Clinical Bottom Line

For healthy adult runners, L-citrulline supplementation cannot be recommended as an effective ergogenic aid based on the current evidence. The most recent systematic review and high-quality trials show no significant benefit for endurance performance 1, 2. Runners seeking performance enhancement should prioritize evidence-based strategies including proper carbohydrate intake (30-60 g/hour during events >1 hour), adequate hydration (limiting weight loss to 2-3%), and carbohydrate loading for events >1.5 hours 7. If L-citrulline is used despite limited evidence, doses of 2.4-8 grams daily for 7-10 days represent the studied protocols, but contraindications include severe renal impairment and potentially baseline hypotension 6, 2, 3.