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L-Citrulline and Sildenafil, a synergy.
L-Citrulline can increase L-arginine availability and nitric-oxide-dependent signaling, which is upstream of sildenafil's PDE5 effect. In a small randomized crossover pilot study, L-citrulline-containing supplementation improved erectile function in men continuing on-demand PDE5 inhibitor therapy. This can be a useful therapeutic synergy, but additive vasodilation may cause flushing, headache, or dizziness.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
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What the row says.
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At a glance
- Substances
- L-Citrulline and Sildenafil
- Pair type
- Synergy
- Evidence (highest tier)
- Emerging
- Source citations
- 2 sources
- Stack Score effect
- +2 to your Stack Score (per scored synergy row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Synergy · Emerging evidence
Synergy
What is happening. L-Citrulline can increase L-arginine availability and nitric-oxide-dependent signaling, which is upstream of sildenafil's PDE5 effect. In a small randomized crossover pilot study, L-citrulline-containing supplementation improved erectile function in men continuing on-demand PDE5 inhibitor therapy. This can be a useful therapeutic synergy, but additive vasodilation may cause flushing, headache, or dizziness.
Mechanism. L-Citrulline increases plasma L-arginine and nitric-oxide signaling. Sildenafil inhibits PDE5 and preserves cGMP in vascular and cavernosal smooth muscle, so the two can act at complementary points in the same vasodilatory pathway.
Recommendation. If you add L-citrulline to sildenafil, start with a low dose and assess tolerability on a day when you can sit or lie down if lightheaded. Avoid nitrates and avoid heavy alcohol use with the combination.
Sources (2)
- Shirai M, Hiramatsu I, Aoki Y, Shimoyama H, Mizuno T, Nozaki T, 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. PMID 30150102
- Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51-59. PMID 17662090
Stack Score
How this pair moves the number.
Effect on the composite score
If both L-Citrulline and Sildenafil are in the same stack, this pair applies +2 to your Stack Score (per scored synergy row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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