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Reviewed by the Scan Dose Research Team and Clinical Advisory Board

Citrulline

STRONG EVIDENCEAmino AcidLast updated April 2026

SCAN DOSE SUMMARY

L-Citrulline is an amino acid that converts to L-arginine in the kidneys, raising blood arginine and nitric oxide levels more effectively than arginine supplementation itself (oral arginine undergoes extensive first-pass metabolism). Our research shows solid evidence for blood pressure reduction, exercise endurance, and erectile function improvement — all via enhanced nitric oxide production. One of the most pharmacologically predictable supplements available.

EVIDENCE GRADES

Blood pressure reductionStrong — meta-analysis of 7 RCTs (PMID: 27866142)
B+
Exercise endurance/performanceModerate — reduced fatigue, improved reps to failure
B
Erectile dysfunctionModerate — small trials but consistent (PMID: 21195829)
B-
Muscle soreness (DOMS)Moderate — citrulline malate specifically
B-
Arginine/NO bioavailabilityDefinitive — pharmacokinetic confirmation
A

WHAT IT DOES

L-Citrulline is produced as a byproduct of nitric oxide synthesis (arginine → NO + citrulline) and recycled back to arginine in the kidneys via the arginine-citrulline cycle. Supplemental citrulline effectively raises plasma arginine levels by 30-50% — more than oral arginine itself, which is extensively metabolized by arginase in the gut and liver.

Higher arginine availability means more substrate for nitric oxide synthase (eNOS), producing more NO. Nitric oxide is a potent vasodilator — it relaxes blood vessel walls, reducing blood pressure, improving blood flow to muscles (exercise performance) and erectile tissue.

Citrulline malate (citrulline bonded to malic acid) is the most common exercise form. The malate may contribute to aerobic energy production via the TCA cycle, though this is secondary to the NO mechanism.

OPTIMAL DOSAGE

  • Blood pressure / cardiovascular: 3-6g/day L-citrulline
  • Exercise performance: 6-8g citrulline malate (contains ~3.4g citrulline per 6g CM)
  • Erectile function: 1.5-3g/day L-citrulline
  • Timing for exercise: 60 min pre-workout
  • No loading phase required — effects are acute but also build with chronic use
Scan a supplement containing Citrulline

DRUG INTERACTIONS

PDE5 inhibitors (Viagra, Cialis)Moderate

Both increase NO/vasodilation — additive hypotension risk

Nitrates (nitroglycerin)Severe

Additive NO/vasodilation — severe hypotension risk

Blood pressure medicationsModerate

Additive BP lowering — monitor

AnticoagulantsMinor

NO has mild antiplatelet effects — theoretical additive

SAFETY PROFILE

Drug Interactions

Side Effects

  • Very well tolerated — GI discomfort at very high doses (>10g)
  • No significant adverse effects documented at standard doses

Pregnancy & Lactation

  • L-citrulline is a naturally occurring amino acid. No safety data for supplemental doses during pregnancy.

WADA Status

Not Prohibited

WHO SHOULD BE CAREFUL

HOW SCAN DOSE SCORES THIS

L-Citrulline preferred over L-Arginine for NO boosting (better oral bioavailability)
Citrulline malate: verify 2:1 ratio (citrulline:malate) — some products use 1:1 (less citrulline per gram)
PDE5 inhibitor users (Viagra, Cialis): automatic moderate interaction alert
Nitrate users (nitroglycerin): automatic SEVERE alert
Products underdosed at <3g total citrulline: flag as sub-therapeutic
Many pre-workouts include citrulline at 3-4g — below the 6-8g exercise dose threshold

CLINICAL REFERENCES

1.

Allerton TD et al. L-Citrulline supplementation: impact on cardiometabolic health.

PMID: 27866142

2.

Cormio L et al. Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction.

PMID: 21195829

3.

Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic performance.

PMID: 20386132

4.

Moinard C et al. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns.

PMID: 27749691

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Reviewed by the Scan Dose Research Team and Clinical Advisory Board | Last updated: April 2026

Not medical advice. Based on published clinical research and systematic reviews.

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