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Effects of Arginine Supplementation on Athletic Performance Based on Energy Metabolism: A Systematic Review and Meta-Analysis

Viribay A, Burgos J, Fernández-Landa J, Seco-Calvo J, Mielgo-Ayuso J
Nutrients 2020 12(5):1300

Bibliography

PubMed
PMID 32370176
PubMed Central
PMC7282262
DOI
10.3390/nu12051300
Funding
External funding: none declared
Competing interests
The authors declare no conflict of interest

Study snapshot

DesignSystematic review and meta-analysis (PRISMA + PICOS)
ModelHuman — mostly trained or elite adult athletes (282 of 394 total participants were trained or elite)
Sample394 participants across 18 studies systematically reviewed; 15 studies included in the quantitative meta-analysis
InterventionArginine supplementation (multiple forms — L-arginine, arginine aspartate, and arginine alpha-ketoglutarate/AAKG pooled) vs placebo. Acute protocols 30 minutes to 2 days pre-exercise; chronic protocols 4 to 8 weeks
DurationTrials ranged from single acute doses to 8-week chronic supplementation
EndpointsPrimary: Aerobic performance (≤VO₂max tests — Harvard Step Test, incremental to exhaustion, 16.1 km time trial, cycloergometer endurance); Primary: Anaerobic performance (>VO₂max tests — Wingate Test, RSAT, 1 km time trial, 1RM strength, isokinetic flexion and extension); Secondary: Effective acute dose and timing; Secondary: Effective chronic dose and duration

What the study showed, in plain terms

This 2020 systematic review and meta-analysis pooled 15 randomized placebo-controlled trials of arginine supplementation in humans, drawn from 18 studies identified in the systematic review. The published pooled estimates favored arginine for both aerobic and anaerobic performance, but the evidence is not equally secure across those outcomes.

For aerobic performance, the published estimate was Hedges' g = 0.84 (95% CI 0.12 to 1.56), but heterogeneity was very high (I² = 89%) and the authors' own analysis detected publication bias. For anaerobic performance, the published estimate was smaller: Hedges' g = 0.24 (95% CI 0.05 to 0.43), with I² = 0%. The included studies pooled several formulations, including L-arginine, arginine aspartate and arginine alpha-ketoglutarate, so the analysis cannot establish an AAKG-specific effect.

A 2025 formal comment by Eric Trexler identified methodological problems in the meta-analysis, including outlier handling, confusion between standard errors and standard deviations, and treatment of dependent effects. Viribay and colleagues published a formal reply acknowledging several methodological issues and describing improved practices in later work, but that reply did not provide corrected pooled estimates for the original 2020 arginine meta-analysis. The original effect sizes therefore remain the published estimates, but they should be interpreted cautiously rather than treated as definitive evidence of a large ergogenic effect.

Key findings

Fifteen randomised placebo-controlled trials of arginine supplementation in humans were pooled quantitatively out of 18 identified in the systematic review.

  • Aerobic performance (≤VO₂max): Hedges' g = 0.84 (95% CI 0.12 to 1.56), p = 0.02. The authors classify this as a large effect. Heterogeneity was I² = 89% — a large amount of inconsistency between studies. Egger's test for publication bias was statistically significant (z = 2.873, p < 0.05).
  • Anaerobic performance (>VO₂max): Hedges' g = 0.24 (95% CI 0.05 to 0.43), p = 0.01. The authors classify this as a small effect. Heterogeneity was I² = 0% — no meaningful inconsistency.
  • Effective acute dose: 0.15 g per kg body weight (roughly 10 to 11 g for a 70 kg adult) taken 60 to 90 minutes before exercise.
  • Effective chronic dose: 1.5 to 2 g per day for 4 to 7 weeks for aerobic performance; 10 to 12 g per day for 8 weeks for anaerobic performance.
  • Formulations pooled: plain L-arginine, arginine aspartate, and arginine alpha-ketoglutarate (AAKG). The meta-analysis did not separate results by formulation.
  • Participants: 394 total (386 male, 8 female). 282 were classified as trained or elite athletes.

What this study can and cannot tell us

Very high heterogeneity affected the primary aerobic result: I² = 89%, meaning the pooled trials were highly inconsistent. A single summary effect therefore masks substantial between-study disagreement.

The authors' own publication-bias analysis was statistically significant for aerobic outcomes (Egger's test z = 2.873, p < 0.05), raising concern that the published literature may overestimate benefit.

A 2025 formal methodological comment identified problems including outlier handling, confusion between standard errors and standard deviations, and handling of dependent effects. Viribay et al. replied and acknowledged several methodological concerns, but the reply did not publish a corrected re-analysis or replacement pooled effect estimates for the original 2020 arginine meta-analysis. The original Hedges' g estimates should therefore be treated as uncertain.

The analysis pooled L-arginine, arginine aspartate and arginine alpha-ketoglutarate rather than estimating formulation-specific effects. It cannot establish that AAKG itself improves performance.

The participant pool was overwhelmingly male (386 men and 8 women) and mostly trained or elite athletes, limiting generalizability to women and less-trained populations.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability