Amino Acid

L-Arginine

2-Amino-5-guanidino-pentanoic acid

Evidence TierCWADA NOT PROHIBITED

tuneTypical Dose

1.5–6 g/day in ED-focused trials. 4–24 g/day ranges used in vascular studies

watchEffect Window

4 weeks to 3 months depending on outcome.

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

L-arginine is an amino acid substrate for nitric oxide synthesis and vascular dilation. It is used for blood flow support, endothelial function goals, and erectile function symptoms.

Studies show modest improvements in endothelial function and small blood pressure reductions in some populations, with potential benefits for mild erectile dysfunction. Exercise performance effects remain inconsistent because oral arginine is limited by substantial first-pass metabolism. Pregnancy-related preeclampsia prevention is the most interesting secondary signal, but it belongs in specialist obstetric care rather than casual supplement use.

L-Arginine supports nitric-oxide signaling as a vasodilatory pathway. Higher oral/systemic exposure is more plausibly linked to hemodynamic effects, but clinical outcomes are population-dependent.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Reduced SBP and DBP in pooled RCTs. Directional ED outcome improvements in selected vasculogenic cohorts
  • Inconsistent or null effects in many performance trials

Secondary Outcomes

  • Possible reduction in pre-eclampsia risk in selected low-certainty studies
  • No robust evidence for universal performance enhancement

Safety

Contraindications and Interactions

Contraindications

  • Recent MI
  • Active unstable cardiovascular/hepatic/renal disease
  • Pregnancy/lactation without specialist supervision

Side effects

  • Bloating
  • Diarrhea
  • Low blood pressure
  • Worsening of herpes outbreaks

Interactions

  • Antihypertensives
  • Nitrates
  • PDE5 inhibitors
  • Potassium-sparing diuretics
  • Anticoagulants

Avoid if

  • Unstable hypotension
  • Recent cardiac event
  • Poor supplement quality context

Evidence

Study-level References

l-arginine-SRC-001Meta-analysis of 11 randomized double-blind, placebo-controlled trials
Sourceopen_in_new

Dong JY et al., Am Heart J. 2011, 10.1016/j.ahj.2011.09.012 (PMID: 22137067)

Population: Adults with oral dosing, n=387

Dose protocol: 4–24 g/day, short to mid-term interventions

Key findings: SBP decreased by ~5.39 mmHg. DBP by ~2.66 mmHg versus placebo

Notes: Moderate. Small heterogeneous RCT set and trial design variability.

Paper content

SBP decreased by ~5.39 mmHg; DBP by ~2.66 mmHg versus placebo

l-arginine-SRC-002Meta-analysis (10 RCTs)
Sourceopen_in_new

Rhim HC et al., J Sex Med. 2019, 10.1016/j.jsxm.2018.12.002 (PMID: 30770070)

Population: Men with mild–moderate ED, n=540

Dose protocol: 1.5–5 g/day across trials, weeks to months

Key findings: Higher response odds for ED outcomes versus control (OR 3.37, 95% CI 1.29–8.77)

Notes: Mildly moderate. Protocol heterogeneity and dosage variability increase interpretability limits.

Paper content

Higher response odds for ED outcomes versus control (OR 3.37; 95% CI 1.29–8.77)

l-arginine-SRC-003Randomized, double-blind, placebo-controlled trial
Sourceopen_in_new

Menafra D et al., J Endocrinol Invest. 2022, 10.1007/s40618-021-01704-3 (PMID: 34973154)

Population: Vasculogenic ED (mild-mod/severe), n=98

Dose protocol: 6 g/day orally, 3 months

Key findings: Improved IIEF-6 scores. Greater benefit in mild-moderate subgroup

Notes: Single-center trial with limited size and subgroup imbalance potential.

Paper content

Improved IIEF-6 scores; greater benefit in mild-moderate subgroup

l-arginine-SRC-004Narrative review with synthesis of RCTs and meta-analyses
Sourceopen_in_new

Park H-Y et al., Nutrients. 2023, 10.3390/nu15051268 (PMCID: PMC10005484; PMID: 36904267)

Population: Recreational/trained adults in cardiovascular and performance studies

Dose protocol: Reported dose-dependent context. Includes 0.075 g/kg Arg and 2.4–6 g/day Cit ranges in cited studies

Key findings: Largely inconsistent for performance. Citrulline signals stronger than arginine in some athletic subgroups

Notes: Not a primary trial dataset. Conclusions limited by source heterogeneity.

Paper content

Largely inconsistent for performance; citrulline signals stronger than arginine in some athletic subgroups

l-arginine-SRC-005Meta-analysis of RCTs and non-RCTs
Sourceopen_in_new

Makama M et al., BJOG. 2025, 10.1111/1471-0528.18070 (PMID: 39800868)

Population: Pregnant people with hypertensive disorder risk, n=2028 in RCTs

Dose protocol: Prenatal intervention timing and dosing varied by trial

Key findings: Reduced pre-eclampsia risk in prevention subset (RR 0.52), evidence rated low/very low for some secondary outcomes

Notes: High risk of bias in 8 RCTs and some concerns in 12 others.

Paper content

Reduced pre-eclampsia risk in prevention subset (RR 0.52), evidence rated low/very low for some secondary outcomes

l-arginine-SRC-006Official anti-doping regulatory document
Sourceopen_in_new

WADA Prohibited List (2026) official resource, WADA website

Population: Athlete eligibility framework (not a clinical trial)

Dose protocol: Annual annualized list, in force 1 Jan 2026

Key findings: No arginine-specific ingredient ban identified in list resources accessed. Classification status must still be checked each season

Notes: Regulatory status is dynamic. User-level risk remains contamination-based even when ingredient not explicitly banned.

Paper content

No arginine-specific ingredient ban identified in list resources accessed; classification status must still be checked each season

l-arginine-SRC-007Regulatory agency consumer guidance
Sourceopen_in_new

FDA. Information for Consumers on Using Dietary Supplements. 2026 update

Population: US supplement market/regulatory context

Dose protocol: Not outcome-based

Key findings: Supplements may be marketed without prior FDA safety/effectiveness approval. Post-market risk persists

Notes: Not efficacy data. Governance context only.

Paper content

Supplements may be marketed without prior FDA safety/effectiveness approval; post-market risk persists

l-arginine-SRC-008Randomized double-blind placebo-controlled clinical trial
Sourceopen_in_new

Camarena Pulido EE, García Benavides L, Panduro Barón JG, Pascoe Gonzalez S, Madrigal Saray AJ, García Padilla FE, et al. Efficacy of L-arginine for preventing preeclampsia in high-risk pregnancies: A double-blind, randomized, clinical trial. Hypertens Pregnancy. 2016;35(2):217-225. doi:10.3109/10641955.2015.1137586. PMID:27003763.

Population: Pregnant patients at high risk for preeclampsia.

Dose protocol: Oral L-arginine started at 20 weeks gestation in high-risk pregnancies.

Key findings: Trial reported fewer preeclampsia cases, higher birth weight, and fewer preterm births versus placebo.

Notes: Strong single-trial signal, but still not enough for unsupervised pregnancy supplementation claims.

Paper content

This is the clearest single randomized pregnancy trial behind arginine's preeclampsia-prevention signal. It found fewer preeclampsia cases and fewer preterm births in a high-risk cohort, but it is still one study in a specialized setting. It supports a cautious pregnancy-research claim, not casual self-use in pregnancy.

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