L-Arginine is a semi-essential amino acid. In the body, it is catalyzed by nitric oxide synthase (NOS) to produce nitric oxide (NO), while also participating in the urea cycle, creatine synthesis, and polyamine production. Its efficacy in enhancing exercise endurance centers on vasodilation, oxygen supply optimization, and energy metabolism regulation. The effects are influenced by exercise type, supplementation dosage, individual variability, and combination strategies, with particularly pronounced benefits observed in endurance-based sports.
I. Core Mechanisms of L-Arginine in Enhancing Exercise Endurance
Promoting Nitric Oxide Production to Improve Blood Circulation and Oxygen SupplyL-Arginine is the sole substrate for endogenous NO synthesis. As a potent vasodilator, NO activates guanylate cyclase in vascular smooth muscle cells, inducing smooth muscle relaxation and subsequent dilation of peripheral blood vessels and skeletal muscle microvasculature. This process significantly boosts skeletal muscle blood flow and oxygen delivery efficiency, reduces peripheral vascular resistance during exercise, and alleviates cardiac pumping load. For endurance sports such as middle- and long-distance running, cycling, and swimming—where skeletal muscle demands for oxygen surge during prolonged contractions—L-arginine-mediated vasodilation alleviates muscle hypoxia and delays fatigue caused by lactic acid accumulation. Studies demonstrate that L-arginine supplementation increases athletes’ skeletal muscle blood flow by 15%–25% and elevates maximal oxygen uptake (VO₂max) by a modest 3%–8%, making it particularly suitable for high-intensity endurance exercises where oxygen supply is a limiting factor.
Optimizing Energy Metabolism to Enhance Muscle Work EfficiencyL-Arginine participates in multiple energy metabolic pathways in the body, improving muscle endurance through both substrate supply and metabolic regulation:
Support for Creatine Synthesis: Creatine is a core substrate for muscle energy storage. L-Arginine, together with glycine and methionine, synthesizes creatine. Supplementation with L-arginine increases intramuscular creatine content, enhances the rapid energy supply capacity of the phosphocreatine system, and delays ATP depletion during high-intensity endurance exercise.
Promoting Glucose and Lipid Metabolism: NO activates AMP-activated protein kinase (AMPK)—a key regulator of energy metabolism—stimulating skeletal muscle glucose uptake and utilization, while accelerating fat catabolism for energy production. This reduces glycogen consumption during exercise and prolongs time to exhaustion in endurance activities.
Reducing Metabolic Acidosis: Exercise-induced lactic acid accumulation and subsequent pH decline are major contributors to fatigue. L-Arginine accelerates lactate transport and clearance by improving blood circulation, while also regulating acid-base balance in skeletal muscle to maintain the physiological environment required for normal muscle contraction.
Inhibiting Oxidative Stress and Inflammatory Responses to Alleviate Post-Exercise FatigueProlonged endurance exercise triggers excessive reactive oxygen species (ROS) production and inflammatory cytokine release, causing muscle cell membrane damage, mitochondrial dysfunction, reduced exercise endurance, and prolonged recovery time. NO derived from L-arginine exhibits antioxidant properties, scavenging free radicals such as superoxide anions generated during exercise and protecting the structural integrity of skeletal muscle cells and mitochondria. Additionally, NO inhibits the nuclear factor κB (NF-κB) pathway, reducing the expression of pro-inflammatory cytokines (e.g., TNF-α, IL-6), mitigating exercise-induced muscle inflammation, accelerating post-exercise muscle function recovery, and enhancing endurance performance in subsequent training sessions.
II. Efficacy Variations Across Different Exercise Scenarios
Endurance Sports (Middle/Long-Distance Running, Cycling, Triathlon)L-Arginine exerts its most significant effects in endurance exercises lasting over 60 minutes. Through improved oxygen supply and optimized energy metabolism, supplementation extends athletes’ time to exhaustion by 10%–20% and reduces post-exercise blood lactate concentrations by 12%–18%. For example, long-distance runners supplemented with L-arginine exhibit lower heart rates and subjective fatigue levels at the same pace, enabling them to sustain higher-intensity exercise for longer durations.
High-Intensity Interval Training (HIIT)HIIT imposes extreme demands on oxygen supply and rapid energy replenishment. L-arginine-mediated vasodilation enhances muscle blood flow during interval recovery periods, accelerating metabolic waste clearance and allowing athletes to maintain better performance in subsequent high-intensity intervals. Research indicates that athletes supplemented with L-arginine complete 8%–12% more repetitions during HIIT sessions, with significantly reduced post-exercise muscle soreness.
Strength-Based SportsStrength sports rely on short-duration, high-intensity muscle contractions, with relatively low endurance requirements. Thus, L-arginine has limited direct effects on performance enhancement. However, by promoting creatine synthesis and improving muscle microcirculation, it can increase the volume of strength training (i.e., more sets and repetitions), indirectly laying the foundation for muscle growth.
III. Key Supplementation Strategies and Precautions for L-Arginine
Supplementation Dosage and Timing
Recommended Dosage: 3–6 g per day during regular training periods; this can be increased to 6–10 g per day during pre-competition intensification, administered in 2–3 divided doses. Excessive supplementation (>15 g per day) may cause gastrointestinal discomfort (e.g., bloating, diarrhea), headaches, or blood pressure fluctuations—blind dose escalation should be avoided.
Optimal Timing: Supplementing 60–90 minutes before exercise maximizes NO levels during physical activity. Post-exercise supplementation combined with carbohydrates and protein promotes muscle recovery while synergistically enhancing energy metabolism efficiency.
Combination Strategies to Enhance EfficacyL-Arginine produces synergistic effects when combined with specific nutrients, amplifying its endurance-boosting benefits:
Combination with L-Citrulline: L-Citrulline promotes the recycling and reuse of L-arginine, reduces its catabolism in the liver, and elevates plasma L-arginine concentrations. Co-supplementation yields superior results compared to L-arginine alone, with common ratios of 1:1 or 2:1 (L-citrulline:L-arginine).
Combination with Antioxidants: Antioxidants such as vitamin C and vitamin E protect NO from free radical degradation, prolonging its biological half-life and enhancing vasodilatory effects.
Combination with Carbohydrates: Carbohydrates stimulate insulin secretion, accelerating the transport of L-arginine into skeletal muscle cells and improving its intramuscular utilization rate.
Individual Variability in EfficacyThe effects of L-arginine vary significantly among individuals:
Training Level: Novice athletes with no systematic training experience experience more pronounced benefits, whereas elite athletes—whose endogenous NO synthesis systems are already highly active—exhibit relatively modest improvements.
Genetic Factors: Some individuals carry NOS gene polymorphisms that reduce their responsiveness to L-arginine, resulting in suboptimal supplementation effects.
Health Status: Patients with hypertension or kidney disease should supplement with caution to avoid exacerbating bodily burden. Individuals with hypotension may experience dizziness or fatigue and should adjust dosage or discontinue supplementation accordingly.
L-Arginine demonstrates clear efficacy in enhancing endurance performance through mechanisms such as promoting NO production, optimizing oxygen supply and energy metabolism, and inhibiting oxidative stress. It is a valuable nutrient for athletes seeking to improve endurance and accelerate post-exercise recovery.