L-Citrulline
Specifically for Erectile Dysfunction
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Why it works for Erectile Dysfunction:
Restores nitric-oxide (NO) supply to the penis. Penile erection depends on NO-mediated relaxation of cavernosal smooth muscle; low NO bioavailability is a core pathway in many cases of ED. ScienceDirect
Citrulline → arginine → NO. Oral L-citrulline is converted in the kidneys to L-arginine, the substrate for NO synthase. Importantly, citrulline bypasses intestinal/liver “first-pass” metabolism that limits oral arginine, so it raises plasma arginine and NO-signaling more reliably and in a dose-dependent way. BPS Publications
How to use for Erectile Dysfunction:
Monotherapy for mild ED
• Dose used: 1.5 g/day of L-citrulline (elemental, not citrulline malate) for 1 month.
• Outcome measures: Erection Hardness Score (EHS), intercourse frequency, satisfaction.
• Result: More men achieved normal EHS on citrulline than on placebo, with no significant adverse events reported in this small pilot. Europe PMC
Adjunct when PDE5 inhibitors are underperforming
• Dose used: L-citrulline 800 mg/day + trans-resveratrol 300 mg/day for 1 month, while continuing on-demand PDE5 inhibitors (e.g., sildenafil).
• Result: Improved SHIM (IIEF-5) scores vs placebo in a randomized, double-blind crossover pilot. ScienceDirect
General administration notes (from the above literature & pharmacology):
• Can be taken once daily; some clinicians split into AM/PM to improve GI tolerance.
• Take consistently for several weeks; studies assessed outcomes after ~4 weeks.
• Because citrulline can lower blood pressure, be cautious combining with other vasodilators (see Warnings). BPS Publications
Scientific Evidence for Erectile Dysfunction:
Pilot RCT (monotherapy): 24 men with mild ED crossed over between placebo (1 month) and L-citrulline 1.5 g/day (1 month). EHS normalization occurred in 50% on citrulline vs 8.3% on placebo, with increased monthly intercourse frequency and no significant adverse events. (Small, single-blind.) Europe PMC
Pilot RCT (adjunct to PDE5i): Men with suboptimal response to PDE5 inhibitors received citrulline 800 mg/day + trans-resveratrol 300 mg/day vs placebo for a month in a double-blind crossover; SHIM scores improved on active treatment. (Small, combination product; not citrulline alone.) ScienceDirect
Human pharmacology: Multiple controlled studies in healthy adults show oral citrulline increases plasma arginine and augments NO-dependent signaling better than oral arginine—supporting the biologic rationale. BPS Publications
Guidelines context: Major urology guidelines (AUA/EAU) do not list citrulline as first-line ED therapy; PDE5 inhibitors, risk-factor control, and other modalities remain standard. (You and your clinician can consider nutraceuticals as adjuncts in select cases.) AUANews
Specific Warnings for Erectile Dysfunction:
Drug interactions / additive hypotension
• Antihypertensives: Citrulline may add to BP-lowering effects. Monitor for dizziness, lightheadedness; discuss with your prescriber if you’re on BP meds. WebMD
• PDE5 inhibitors (sildenafil, tadalafil, etc.): Each can lower BP; stacking vasodilators may increase hypotension risk—especially at higher doses. Use together only under clinician guidance. WebMD
• Nitrates (e.g., nitroglycerin) or nicorandil: PDE5 inhibitors are absolutely contraindicated with nitrates due to dangerous hypotension; because citrulline is also a vasodilatory NO-pathway agent, do not experiment with combinations of nitrates + PDE5i + citrulline—talk to your cardiologist first. NICE
Surgery: Stop ~2 weeks before planned procedures (potential BP effects). WebMD
Pregnancy/breastfeeding: Insufficient safety data—avoid. WebMD
Side effects seen in studies/monographs: Usually mild—GI upset, heartburn. Most trials are short-term (weeks); long-term safety data are limited. WebMD
Quality matters: Use third-party–tested products (USP/NSF/ConsumerLab) because supplements are not regulated like prescription drugs. Verywell Health
General Information (All Ailments)
What It Is
L-Citrulline is a non-essential amino acid, meaning the body can produce it naturally. It was first identified in watermelon (Citrullus vulgaris), which is where it gets its name. Unlike essential amino acids, L-citrulline isn’t directly incorporated into proteins. Instead, it serves as a precursor to other important compounds, most notably L-arginine and nitric oxide (NO), both of which play significant roles in cardiovascular and muscular health.
It can be found naturally in foods such as watermelon, cucumbers, and pumpkins, and it’s also available as a dietary supplement—either in pure form or as L-citrulline malate (a combination of citrulline and malic acid, often used to enhance exercise performance).
How It Works
L-Citrulline functions mainly through its conversion into L-arginine in the kidneys. L-arginine then serves as a substrate for the enzyme nitric oxide synthase (NOS), which generates nitric oxide (NO)—a critical molecule for vasodilation (the widening of blood vessels).
By increasing nitric oxide levels, L-citrulline can help improve blood flow, oxygen delivery, and nutrient transport to tissues. This mechanism has several downstream effects:
- Improved Exercise Performance: Enhanced blood flow delivers more oxygen and nutrients to working muscles, potentially reducing fatigue and improving endurance.
- Cardiovascular Health: Better endothelial (blood vessel) function may help reduce blood pressure and support overall heart health.
- Enhanced Recovery: Increased circulation may assist in clearing metabolic waste (like ammonia and lactic acid) from muscles after intense exercise.
- Erectile Function: Improved nitric oxide availability can aid in relaxing blood vessels, a mechanism similar to that of erectile dysfunction medications.
An additional pathway involves ammonia clearance. L-citrulline plays a role in the urea cycle, which helps the body eliminate ammonia, a toxic byproduct of protein metabolism. This contributes to improved recovery and reduced muscle fatigue.
Why It’s Important
L-Citrulline’s importance lies in its broad range of physiological benefits, especially for vascular, muscular, and metabolic health:
- Supports Cardiovascular Function: Through nitric oxide production, it helps maintain healthy blood pressure and vessel elasticity.
- Enhances Exercise Performance: Studies show it may delay fatigue, improve endurance, and increase strength output, particularly in resistance training and high-intensity workouts.
- Promotes Muscle Recovery: Its role in ammonia detoxification and improved blood flow helps accelerate recovery between training sessions.
- May Aid Sexual Health: Because it enhances circulation, L-citrulline has been researched as a natural aid for mild erectile dysfunction.
- Supports General Energy Metabolism: The malate component in citrulline malate contributes to the Krebs cycle (the body’s primary energy production pathway), potentially improving overall energy availability.
Considerations
While L-citrulline is generally considered safe and well-tolerated, there are several points to consider before use:
Dosage:
- Typical doses range from 3 to 6 grams per day for general circulatory or cardiovascular support.
- For exercise performance, studies often use 6 to 8 grams of L-citrulline malate taken 30–60 minutes before training.
Possible Side Effects:
- Most people experience no adverse effects, but mild gastrointestinal discomfort (bloating or nausea) can occur at higher doses.
- Because it can lower blood pressure, individuals already on antihypertensive medications should consult a healthcare professional.
Interactions:
- Combining L-citrulline with other nitric oxide boosters (like L-arginine or beetroot extract) may enhance its effects—but also potentially lower blood pressure more than desired.
- Those taking nitrate medications (e.g., for heart disease) should use caution.
Form and Purity:
- L-Citrulline Malate is often preferred for performance purposes due to better absorption and synergistic energy benefits.
- Always select third-party tested supplements to ensure purity and correct dosing.
Long-Term Use:
- Research supports its safety in both short- and medium-term use (up to 12 months), but long-term studies are still limited.
- Its effects may vary between individuals depending on diet, fitness level, and baseline nitric oxide status.
Helps with these conditions
L-Citrulline is most effective for general wellness support with emerging research . The effectiveness varies by condition based on clinical evidence and user experiences.
Detailed Information by Condition
Erectile Dysfunction
Restores nitric-oxide (NO) supply to the penis. Penile erection depends on NO-mediated relaxation of cavernosal smooth muscle; low NO bioavailability...
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