NutriStack
L-Arginine and Sildenafil, a caution.
L-arginine is a nitric oxide precursor, and sildenafil enhances NO/cGMP signaling by inhibiting PDE5. Combined use can cause additive vasodilation and significant hypotension.
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.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- L-Arginine and Sildenafil
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 4 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Moderate evidence
Caution
What is happening. L-arginine is a nitric oxide precursor, and sildenafil enhances NO/cGMP signaling by inhibiting PDE5. Combined use can cause additive vasodilation and significant hypotension.
Mechanism. L-arginine → NO (via eNOS) → activates guanylyl cyclase → cGMP → vasodilation. Sildenafil inhibits PDE5, preventing cGMP breakdown. The combination amplifies the NO/cGMP vasodilatory cascade.
Recommendation. Use caution when combining. Start L-arginine at low doses. Monitor for headache, dizziness, flushing, and low blood pressure. Do NOT combine with nitrates.
Sources (4)
- Stanislavov R, Nikolova V. Treatment of erectile dysfunction with pycnogenol and L-arginine. J Sex Marital Ther. 2003;29(3):207-213. PMID 12851125
- Viribay A, Burgos J, Fernández-Landa J, Seco-Calvo J, Mielgo-Ayuso J. Effects of Arginine Supplementation on Athletic Performance Based on Energy Metabolism: A Systematic Review and Meta-Analysis. Nutrients. 2020. PMID 32370176
- Rezaei S, Gholamalizadeh M, Tabrizi R et al.. The effect of L-arginine supplementation on maximal oxygen uptake: A systematic review and meta-analysis. Physiological Reports. 2021. PMID 33587327
- Hadi A, Arab A, Moradi S et al.. The effect of l-arginine supplementation on lipid profile: a systematic review and meta-analysis of randomised controlled trials. British Journal of Nutrition. 2019. PMID 31922465
Stack Score
How this pair moves the number.
Effect on the composite score
If both L-Arginine and Sildenafil are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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