✓ No active regulatory warningsFDA MedWatch, EMA EudraVigilance, WHO VigiBase, WADA Prohibited List · 2026-05-29
📰Read the full Citrulline Malate evidence review on GMJ News →Complete clinical article, references and updates on news.gmj.ge. This page is the structured safety summary.⚠ PDE5 inhibitor + citrulline — additive NO → hypotension [1]
⚠ Better NO precursor than arginine itself [1]
⚠ Citrulline malate 6–8 g for exercise; L-citrulline 3–6 g for BP [2]
ℹ️ Not obtained from food. Not applicable as a daily target — obtained as part of dietary protein rather than tracked individually.
🔬 Lab interpreter
Recommended test
Blood pressure
Blood pressure
Reference range / target
Reduction from baseline
Reduction from baseline
~4 mmHg SBP reduction [1].
Full lab monitoring ↓⚕ For professionals — confirm ranges against your local laboratory.
Clinical verdict
Citrulline is a BETTER arginine/NO precursor than arginine itself (bypasses hepatic arginase, raises plasma arginine 2×). Citrulline malate 6–8 g pre-workout for exercise. L-citrulline 3–6 g/day for BP. Mild ED: 1.5 g/day (one trial). Do NOT combine with PDE5 inhibitors or nitrates (hypotension) [1] [2].
1 How much do I need?
👤 Adults: Specific dosage data under clinical review
👴 Elderly: Specific dosage data under clinical review
🤰 Pregnancy: See guidance
Normal amino acid. No supplementation data [1].
👦 Pediatric: See guidance
Limited data [1].
🏃 Athletes: Standard dose
⚖️ Obesity: Standard dose
Fat-soluble compounds may require dose adjustment in obesity.
🩺 Renal: Consult specialist
Dose adjustment may be needed in renal impairment.
🌱 Vegan: Standard dose
How to take
💊 With food: With or without food [1].
🚫 Avoid: PDE5 inhibitors, nitrates (hypotension) [1].
2 Which form?
| Form | Bioavailability | Vegan | Cost |
|---|---|---|---|
| ['L-Citrulline', 'common', 'Pure citrulline. 3–6 g/day. For BP/NO/erectile function [1].'] | Standard | Check label | |
| ['Citrulline Malate 2:1', 'preferred', 'Citrulline + malic acid. 6–8 g pre-workout. Most exercise studies [2].'] | Standard | Check label |
3 Common questions
Why citrulline instead of arginine? ▼
Oral arginine undergoes extensive hepatic first-pass metabolism by arginase — much of it is broken down before reaching systemic circulation. Citrulline bypasses the liver and is converted to arginine in the kidneys. Citrulline raises plasma arginine 2× more than equivalent arginine [1].
Citrulline vs citrulline malate? ▼
Citrulline malate (2:1) adds malic acid (Krebs cycle intermediate). Most exercise studies used citrulline malate. For BP/vascular effects, pure L-citrulline is fine [2].
Does citrulline help ED? ▼
One trial showed 1.5 g/day improved erection hardness in mild ED. Less potent than PDE5 inhibitors but a reasonable natural first option for mild ED [1].
4 Clinical evidence
Strong
Citrulline raises plasma arginine more effectively than oral arginine (bypasses hepatic arginase) [1]. Citrulline → arginine → NO pathway: well-established biochemistry [1]. HIGH
Moderate
Exercise: citrulline malate 6–8 g improved reps to failure, reduced muscle soreness, and enhanced high-intensity exercise capacity in multiple trials [2]. Blood pressure: meta-analysis showed ~4 mmHg SBP reduction with L-citrulline [1]. Erectile dysfunction: one trial showed L-citrulline 1.5 g/day improved erection hardness (mild ED) [1]. MODERATE
Insufficient
5 Safety, toxicity & adverse events
Absolute contraindications
✕ Concurrent nitrates or PDE-5 inhibitors — additive blood-pressure lowering
Relative
⚠ Antihypertensives — additive effect
⚠ Low blood pressure
🚩 Red flags
● PDE5 inhibitor + citrulline — hypotension [1]
● Nitrate (GTN) + citrulline — dangerous hypotension [1]
6 Interactions
Drug interactions
PDE5 inhibitors (sildenafil) Major
Mechanism: Both enhance NO-mediated vasodilation. Additive. [1]
Effect: Hypotension, syncope. [1]
Action: Do not combine without physician guidance [1].
Nitrates Major
Mechanism: Additive NO vasodilation. [1]
Effect: Severe hypotension. [1]
Action: AVOID [1].
Supplement synergies
Beetroot juice/nitrate · 6–12 mmol nitrate
Dual-pathway NO: citrulline (arginine→NO) + nitrate (NO₃→NO₂→NO) [1].
Dual-pathway NO: citrulline (arginine→NO) + nitrate (NO₃→NO₂→NO) [1].
Creatine + Beta-Alanine · Standard doses each
Comprehensive pre-workout stack (NO + ATP + pH buffer) [2].
Comprehensive pre-workout stack (NO + ATP + pH buffer) [2].
7 Regulatory
United States: GRAS. Dietary supplement [1].
WADA: Not prohibited [2].
8 US supplement products
135
on-market products containing Citrulline Malate (NIH DSLD)
Brands carrying Citrulline Malate (57)
Click a brand to see its Citrulline Malate products.
9 Frequently paired with
10 Cite this page
Vancouver: Pkhakadze G. Citrulline Malate — safety profile [Internet]. Tbilisi: PHIG; 2026 [cited 2026 Oct 16]. Available from: https://supplement.ge/ingredients/citrulline-malate/
APA 7th: Pkhakadze, G. (2026). Citrulline Malate — Safety profile. Public Health Institute of Georgia. https://supplement.ge/ingredients/citrulline-malate/
📋 Editorial information
Author: Prof. G. Pkhakadze, MD, MPH, PhD
Institution: Public Health Institute of Georgia (PHIG)
Affiliation: David Tvildiani Medical University (DTMU)
First published: January 2026
Last reviewed: 2026-05-29
Next review: April 2027
References: 2 cited sources
COI: SupplementIndex receives no funding from supplement manufacturers. All content independently authored by PHIG.
Process: Systematic literature review
📄 License & reuse
Published under Creative Commons Attribution 4.0 International (CC BY 4.0). You may share and adapt for any purpose with attribution.
Pkhakadze G. "Citrulline Malate — Safety Profile." SupplementIndex, PHIG, 2026. https://supplement.ge/ingredients/citrulline-malate/ CC BY 4.0.
GP
Prof. G. Pkhakadze, MD, MPH, PhD
Professor of Public Health · Head of Department, DTMU
Editor-in-Chief, Georgian Medical Journal (ISSN 3088-4322)
Chair, Public Health Institute of Georgia · UEMS Public Health Section
Educational and public health purposes. CC BY 4.0. Consult your healthcare provider before starting any supplement. Corrections: info@accreditation.ge. Publisher: PHIG