L-Arginine for Nitric Oxide Production

Oral L-arginine is largely degraded before reaching circulation, so NO effects are small and inconsistent.

Overview

Oral L-arginine is largely degraded before reaching circulation, so NO effects are small and inconsistent.

Verdict

Not supported

Poor oral bioavailability makes it the wrong choice - use citrulline.

How It Works

Arginine is the direct eNOS substrate, but intestinal and hepatic arginase destroy most of an oral dose.

Dosing & Protocol

Typical dose

Recommended dose: Not recommended; use citrulline instead
Expected timeframe: n/a

Protocol

safety: Do not use with nitrates or after a recent heart attack
instead: L-citrulline 6-8 g bypasses first-pass metabolism and raises plasma arginine higher at a lower dose; dietary nitrate from beetroot is the other validated route
studied dose: 3-9 g/day oral L-arginine
evidence note: Verdict is no - oral arginine is a poor way to raise nitric oxide
what happened: Effects on flow-mediated dilation and performance were inconsistent, because most oral arginine is destroyed by intestinal and hepatic arginase before it reaches circulation. A post-myocardial-infarction trial was stopped early for safety

Evidence

What the studies say

Trials of oral arginine show inconsistent effects on flow-mediated dilation and exercise performance, and a post-myocardial-infarction trial was stopped early for safety concerns. Citrulline achieves higher plasma arginine at lower doses.

Oral L-arginine supplementation and endothelial function: a meta-analysis of randomized controlled trials

Score: 7/10

2009

meta_analysis

n=387

Bai Y, Sun L, Yang T +3 more

L-arginine improved flow-mediated dilation, but benefit was confined to impaired baseline endothelial function

View source

L-arginine supplementation fails to improve outcomes after acute myocardial infarction: the VINTAGE MI randomized trial

Score: 8/10

2006

rct

n=153

Schulman SP, Becker LC, Kass DA +3 more

L-arginine did not improve vascular stiffness and was associated with more deaths

View source

Safety

Caveats

Avoid after recent myocardial infarction; may trigger herpes reactivation in susceptible people.

Less likely to help if

Almost everyone taking oral arginine for nitric oxide, because of arginase-driven first-pass loss.

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