NutriStack
L-Citrulline and Tadalafil, a synergy.
L-Citrulline can raise plasma L-arginine and nitric-oxide signaling, while tadalafil preserves cGMP by inhibiting PDE5. A small randomized crossover pilot study found that L-citrulline-containing supplementation improved erectile function in men who were still using on-demand PDE5 inhibitors. The combination is usually a therapeutic synergy, but dizziness or flushing can occur if vasodilation becomes excessive.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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At a glance
- Substances
- L-Citrulline and Tadalafil
- 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 raise plasma L-arginine and nitric-oxide signaling, while tadalafil preserves cGMP by inhibiting PDE5. A small randomized crossover pilot study found that L-citrulline-containing supplementation improved erectile function in men who were still using on-demand PDE5 inhibitors. The combination is usually a therapeutic synergy, but dizziness or flushing can occur if vasodilation becomes excessive.
Mechanism. L-Citrulline is converted to L-arginine and augments nitric-oxide-dependent signaling. Tadalafil inhibits PDE5, reducing cGMP breakdown, so increased nitric oxide upstream and preserved cGMP downstream can complement erectile-response signaling.
Recommendation. Use L-citrulline with tadalafil only after you know how tadalafil affects your blood pressure. Start with a low L-citrulline dose, avoid combining it with nitrates or heavy alcohol use, and stop the supplement if you develop dizziness, faintness, or severe headache.
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 Tadalafil 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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