L-Citrulline Boosts Endurance in Trained Men

clinical-trial PMID: 37125500

L-Citrulline Boosts Endurance in Trained Men

Quick Summary: A clinical trial tested if L-citrulline combined with glutathione improves endurance and blood flow during intense workouts in young, fit men. After eight days of taking the supplement, participants lasted 13% longer in high-intensity runs and showed better blood flow recovery afterward. This combo raised key amino acid levels in the blood, potentially aiding performance.

What The Research Found

Researchers looked at how L-citrulline—a natural amino acid that helps blood vessels widen—and glutathione—an antioxidant that supports cell health—work together to boost workout stamina. The study showed clear benefits for endurance and recovery, but only in specific scenarios.

Key results include:
- Longer workout time: Men taking the supplement ran 13.4% longer before tiring out during runs at their peak speed (100% effort level). This was a real improvement compared to a fake pill (p=0.048).
- Better blood flow: 30 minutes after exercise, blood flow in the arm's main artery increased significantly (p=0.035), helping muscles recover faster by delivering more oxygen and nutrients.
- Higher amino acid levels: The supplement doubled L-citrulline levels in the blood (2.3 times higher, p<0.001) and boosted L-arginine (1.4 times higher, p=0.002). These changes likely widen blood vessels and improve oxygen use during exercise.
- No big changes at other intensities: It didn't help much for easier (90% effort) or harder (110% effort) runs, suggesting it's best for steady, high-effort workouts.

Overall, the combo seems to enhance aerobic performance by improving circulation and energy delivery to muscles.

Study Details

This was a solid scientific setup: a randomized, double-blind, placebo-controlled crossover trial, meaning participants tried both the real supplement and a fake one, with neither them nor researchers knowing who got what until the end. It ensured fair results.

Who was studied: 25 healthy, trained young men (average age 22 years, height 5'10", weight 166 lbs). These were active guys used to intense exercise, like runners or athletes.
How long: Baseline tests first, then eight straight days of taking the supplement or placebo. A two-week break followed before switching treatments. Testing happened right after the eight days.
What they took: The active blend (Setria Performance Blend) included 2 grams of L-citrulline plus 200 mg of glutathione, split into six capsules taken daily. The placebo was six capsules of harmless cellulose (like plant fiber) weighing about 3.1 grams total.

Tests involved treadmill runs to exhaustion at different speeds, plus ultrasound scans of arm blood vessels and blood samples before, during, and after workouts.

What This Means For You

If you're a fit guy in your 20s pushing hard in cardio workouts like running or cycling, this supplement might help you go longer without fatigue—especially at your max sustainable pace. The blood flow boost could mean quicker recovery between sessions, reducing soreness.

Practical tips:
- Try it for endurance training: Start with 2g L-citrulline + 200mg glutathione daily for a week before big workouts. It could amp up your nitric oxide (a natural blood vessel relaxer) for better performance.
- Who might benefit: Trained athletes aiming to shave seconds off race times or extend training sessions. Untrained folks or women might see different results—more research needed.
- Safety note: It's generally safe short-term, but check with a doctor if you have blood pressure issues, as it affects circulation. Combine with a balanced diet for best results; don't rely on supplements alone.

This isn't a magic pill, but it could give a real edge for high-intensity aerobic efforts.

Study Limitations

No study is perfect, and this one has some caveats to consider before jumping in.

Limited to young men: Only fit guys in their early 20s were tested, so it may not apply to women, older adults, beginners, or other groups.
Short-term only: Just eight days of use; we don't know about longer effects or safety over months.
Missing details: Didn't measure nitric oxide directly or muscle oxygen levels, so the "why" behind benefits isn't fully clear. Also, the supplement came from the maker, which could bias results slightly.
Not for all workouts: Benefits were specific to moderate-high intensity; it won't help every type of exercise.

For broader advice, look at more studies or talk to a trainer. Source: NCT04090138, published in Journal of the International Society of Sports Nutrition (2023).

Key Findings

The study found that acute ingestion of L-citrulline (2 g) + glutathione (200 mg) for eight days significantly increased brachial artery blood flow 30 minutes post-exercise (p=0.035) and plasma concentrations of L-citrulline (2.3-fold increase, p<0.001) and L-arginine (1.4-fold increase, p=0.002) compared to placebo. Time-to-exhaustion (TTE) at 100% peak velocity (PV) was prolonged by 13.4% with the supplement (p=0.048), but no differences were observed at 90% or 110% PV.

Study Design

This was a randomized, double-blind, placebo-controlled crossover clinical trial involving 25 healthy, trained males (mean age: 22.2±2.4 years). Participants underwent baseline testing, then completed two treatment phases (eight days of SPB or placebo) separated by a 14-day washout. Outcomes included treadmill TTE tests at varying intensities, brachial artery blood flow/vessel diameter (via ultrasound), and blood analytes measured pre- and post-exercise at multiple time points.

Dosage & Administration

The supplement (Setria Performance Blend: SPB) comprised 2 g L-citrulline + 200 mg glutathione in six capsules daily. Placebo was 3.1 g cellulose in six capsules. Participants ingested the supplements for eight consecutive days before testing.

Results & Efficacy

Blood Flow: SPB increased brachial artery blood flow at 30minPEX (p=0.035, effect size not reported).
Plasma Concentrations: SPB elevated L-citrulline by 2.3-fold (p<0.001) and L-arginine by 1.4-fold (p=0.002) post-exercise compared to placebo.
Endurance Performance: TTE at 100% PV improved by 13.4% with SPB (p=0.048), but no significant effects were seen at 90% or 110% PV.
Statistical Significance: All reported outcomes met significance thresholds (p<0.05), though confidence intervals were not detailed.

Limitations

Sample Specificity: Participants were young, trained males; findings may not generalize to females, older adults, or untrained populations.
Short Duration: Only eight days of supplementation were tested; long-term effects and safety remain unclear.
Mechanistic Gaps: The study measured blood flow and amino acid concentrations but did not directly assess nitric oxide levels or muscle oxygenation.
Potential Funding Bias: The supplement was provided by a manufacturer (Setria), which may influence outcomes.
Placebo Composition: Cellulose was used as a placebo, but its inertness relative to active treatment was not validated.

Clinical Relevance

For trained males, eight-day supplementation with L-citrulline (2 g) + glutathione (200 mg) may enhance post-exercise blood flow and endurance during high-intensity aerobic activity (~100% PV). However, the lack of performance benefits at lower (90% PV) or higher (110% PV) intensities suggests dose or duration may need optimization. Users should consider individual variability and consult further research on long-term use and broader populations. The combination’s efficacy might be synergistic, as glutathione could enhance L-citrulline’s bioavailability, though standalone effects of L-citrulline alone were not tested.

Source: NCT04090138 | Published in J Int Soc Sports Nutr (2023).