The dose-effect analysis of L-arginine on athletic endurance

The efficacy of L-Arginine in enhancing exercise endurance exhibits significant dose dependence, with its core mechanisms centered on nitric oxide (NO) synthesis, energy metabolism regulation, and oxidative stress alleviation. The physiological effects vary markedly across different dosage ranges, and are influenced by exercise type, individual metabolic characteristics, and supplementation strategies, presenting distinct effective dosage windows and excess thresholds.

I. Correlation Between Dosage Effects and Core Mechanisms

The dose-dependent effects of L-Arginine essentially reflect the dose-response relationship between endogenous NO synthesis rate and metabolic pathway activation, where different dosages correspond to varying activation states of physiological targets:

Low-Dosage Range: Primarily supplements the substrate for endogenous NO synthesis, mildly activating the vasodilation pathway. At this range, the increase in plasma L-Arginine concentration is limited, and nitric oxide synthase (NOS) remains unsaturated, resulting in only a slight elevation of skeletal muscle blood flow and oxygen supply, with a moderate improvement in endurance.

Medium-Dosage Range: NOS is fully activated, NO production reaches its peak, and the vasodilatory effect, energy metabolism regulation, and antioxidant capacity simultaneously achieve optimal states—making this the core dosage range for enhancing exercise endurance.

High-Dosage Range: Excessive L-Arginine triggers metabolic shunting, where part of the substrate is diverted to the urea cycle or polyamine synthesis pathways, leading to decreased NO production efficiency. Meanwhile, surplus arginine competitively inhibits the absorption of other amino acids (e.g., lysine, ornithine), disrupts protein metabolism, and may even induce physiological discomfort, thereby impairing the endurance-enhancing effect.

II. Effect Characteristics and Applicable Scenarios of Different Dosage Ranges

Low-Dosage Range (1–3 g/day): Basic Maintenance and Mild ImprovementThis dosage serves as a supplement for daily physiological needs, suitable for recreational exercisers or during low-intensity training periods.

Physiological Effects: Plasma L-Arginine concentration increases by 10%–20%, NOS activity is mildly activated, skeletal muscle blood flow rises by 5%–10%, and the improvement in maximal oxygen uptake (VO₂max) is less than 3%. It only delays fatigue during low-intensity exercises (e.g., jogging, brisk walking) and does not significantly enhance performance in high-intensity endurance sports.

Advantages and Limitations: High safety profile with no side effects such as gastrointestinal discomfort; however, the endurance-enhancing effect is limited and cannot meet the high-intensity training demands of athletes.

Medium-Dosage Range (3–6 g/day): Core Effective Dosage Window for Endurance EnhancementThis is the optimal dosage for athletes to improve endurance, suitable for endurance sports lasting over 60 minutes (e.g., middle/long-distance running, cycling, triathlon) and high-intensity interval training (HIIT).

Physiological Effects: Plasma L-Arginine concentration increases by 30%–50%, NOS reaches saturated activation, NO production rises significantly, skeletal muscle blood flow increases by 15%–25%, and VO₂max improves by 3%–8%. Simultaneously, the AMPK pathway is activated, fat catabolism rate increases by 20%–30%, glycogen consumption rate decreases by 10%–15%, time to exhaustion is prolonged by 10%–20%, and post-exercise blood lactate clearance rate is enhanced by 12%–18%.

Refined Applicable Scenarios:

Endurance Training Period: Supplement 2 g 60–90 minutes before exercise and 1–2 g within 30 minutes after exercise, twice daily. This significantly boosts training volume and delays fatigue accumulation.

Pre-Competition Intensification Period: Increase dosage to 5–6 g/day, administered in 3 divided doses. This optimizes oxygen supply and energy metabolism during competitions, enhancing athletic performance.

High-Dosage Range (6–10 g/day): Effect Plateau and Rising RisksAt this dosage, the endurance-enhancing effect plateaus, while the risk of side effects increases significantly. It is only suitable for short-term pre-competition intensification in some elite athletes and is not recommended for long-term use.

Physiological Effects: Plasma L-Arginine concentration increases by more than 50%, but NO production no longer rises significantly with increased dosage; instead, metabolic shunting causes waste of partial substrates. The improvement in VO₂max is not significantly different from that of the 5–6 g/day dosage, and the extension of time to exhaustion only increases by 2%–3%.

Potential Risks:

Gastrointestinal Discomfort: The incidence of bloating and diarrhea exceeds 40%, particularly likely when supplemented on an empty stomach.

Blood Pressure Fluctuations: Excessive NO-induced vasodilation may cause dizziness and fatigue in individuals with hypotension.

Amino Acid Metabolism Interference: Competitive inhibition of lysine absorption may impair muscle protein synthesis with long-term high-dosage supplementation.

Excessive-Dosage Range (>10 g/day): Diminished Effects and Aggravated Side EffectsThis dosage exceeds physiological tolerance limits. It not only fails to enhance endurance but also induces significant physiological disorders, and is strictly prohibited for exercise supplementation.

Adverse Effects:

Sharp Decline in NO Synthesis Efficiency: Most L-Arginine is converted to urea in the liver and excreted, resulting in nutrient waste.

Severe Gastrointestinal Reactions: The incidence of gastrointestinal symptoms exceeds 80%, with nausea and vomiting in severe cases.

Impaired Renal Metabolism: Increased metabolic burden on the kidneys.

Possible Immune Dysfunction: Long-term excessive supplementation may inhibit lymphocyte proliferation.

III. Key Regulatory Factors Affecting Dosage Effects

Exercise Type and IntensityLow-intensity endurance exercise requires a relatively low L-Arginine dosage (3 g/day is sufficient), whereas high-intensity endurance exercise or HIIT demands medium-to-high dosages (5–6 g/day) to yield noticeable effects. Strength sports have low requirements for L-Arginine-mediated endurance enhancement, and the dosage generally does not need to exceed 3 g/day.

Individual Metabolic Characteristics

Training Level: Novice athletes are more sensitive to L-Arginine dosage, and can achieve significant effects with medium-to-low dosages. Elite athletes, with highly active endogenous NOS systems, may require moderately increased dosages (but not exceeding 6 g/day).

Genetic Factors: Individuals with NOS gene polymorphisms (e.g., Glu298Asp mutation) have lower NOS activity and higher L-Arginine requirements, potentially needing 6 g/day to achieve equivalent effects.

Health Status: Patients with hypertension or kidney disease should reduce the dosage (≤ 3 g/day), and individuals with hypotension should avoid high-dosage supplementation.

Supplementation Strategies and Combination Regimens

Timing of Intake: Supplementing 60–90 minutes before exercise maximizes NO levels during physical activity, while post-exercise supplementation is more conducive to recovery. Multiple divided doses yield better effects than a single large dose.

Nutrient Combinations: Co-supplementation with L-Citrulline (at ratios of 1:1 or 1:2) reduces L-Arginine catabolism in the liver and increases plasma concentrations. This allows for appropriate dosage reduction (e.g., 4 g/day L-Arginine combined with 4 g/day L-Citrulline yields better effects than 6 g/day L-Arginine alone). Combining with vitamins C and E protects NO from free radical damage, prolongs its duration of action, and enhances the efficacy of medium-to-low dosages.

IV. Practical Application Principles of Dosage Effects

Individualized Dosage Formulation: Adjust the dosage based on exercise intensity, training level, and physical response, adhering to the core principle of “effectiveness without side effects” and avoiding blind pursuit of high dosages.

Combination of Short-Term Intensification and Long-Term Maintenance: Adopt a medium-to-low maintenance dosage of 3–4 g/day during daily training, increase to 5–6 g/day for short-term intensification 1–2 weeks before competitions, and revert to the maintenance dosage post-competition.

Priority to Combined Supplementation Regimens: Leverage the synergistic effects of L-Arginine with L-Citrulline and antioxidants to enhance efficacy while reducing dosage and side effect risks.

The dose-dependent effects of L-Arginine on exercise endurance exhibit the characteristics of “low dosage with low efficacy, medium dosage with high efficacy, high dosage with plateau effect, and excessive dosage with harm”. The range of 3–6 g/day is the core dosage window that balances effectiveness and safety.