NutriStack
Isosorbide Mononitrate and L-Citrulline, a caution.
L-citrulline increases L-arginine availability and can lower blood pressure through nitric oxide pathways. Isosorbide mononitrate is an organic nitrate with sustained vasodilator effects. Combining them may add to blood pressure lowering, increasing dizziness, headache, flushing, or fainting risk.
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
- Isosorbide Mononitrate and L-Citrulline
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 3 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-citrulline increases L-arginine availability and can lower blood pressure through nitric oxide pathways. Isosorbide mononitrate is an organic nitrate with sustained vasodilator effects. Combining them may add to blood pressure lowering, increasing dizziness, headache, flushing, or fainting risk.
Mechanism. L-citrulline is converted to L-arginine and increases substrate availability for nitric oxide synthase. Isosorbide mononitrate donates nitric oxide downstream, so the shared nitric oxide/cGMP pathway can produce additive vasodilation.
Recommendation. Avoid starting high-dose L-citrulline without telling the prescriber who manages your nitrate therapy. If the combination is approved, monitor sitting and standing blood pressure during the first week and stop the supplement if lightheadedness or low readings develop.
Sources (3)
- Stokes GS, Barin ES, Gilfillan KL, Kaesemeyer WH. Interactions of L-arginine, isosorbide mononitrate, and angiotensin II inhibitors on arterial pulse wave. Am J Hypertens. 2003;16(9 Pt 1):719-724. PMID 12944028
- Schwedhelm E, Maas R, Freese R, 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
- Mirenayat MS, Moradi S, Mohammadi H, Rouhani MH. Effect of L-Citrulline Supplementation on Blood Pressure: a Systematic Review and Meta-Analysis of Clinical Trials. Curr Hypertens Rep. 2018;20(11):98. PMID 30284051
Stack Score
How this pair moves the number.
Effect on the composite score
If both Isosorbide Mononitrate and L-Citrulline 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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