Related Experiment Video
Updated: Jul 6, 2025

Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
Published on: December 16, 2021
Plasma Metabolome Analysis Suggests That L-Arginine Supplementation Affects Microbial Activity Resulting in a
Laurianne Dimina1, Marie Tremblay-Franco2,3, Ambre Deveaux1
1Université Paris-Saclay, AgroParisTech, INRAE, UMR PNCA, Palaiseau, France.
Background:
The effects of supplementation with L-arginine (L-arg), the precursor of nitric oxide (NO), on vascular and cardiometabolic health have largely been explored. Whether other mechanisms of the action of L-arg exist remains unknown, as arginine metabolism is complicated.
Objective:
We aimed to characterize the effect of low dose L-arg supplementation on overall human metabolism both in a fasting state and in response to an allostatic stress.
Methods:
In a randomized, double-blind, crossover study, 32 healthy overweight adults (mean age 45 y) with cardiometabolic risk (fasting plasma triglycerides >150 mg/dL; waist circumference >94 cm [male] or >80 cm [female]) were treated with 1.5 g sustained-release L-arg 3 times/d (4.5 g/d) or placebo for 4 wk. On the last day of treatment, volunteers consumed a high-fat meal challenge (900 kcal, 80% as fat, 13% as carbohydrate, and 7% as protein). Plasma was collected at fasting, 2, 4, and 6 h after the challenge, and the metabolome was analyzed by high-resolution liquid chromatography-mass spectrometry. Metabolic profiles were analyzed using linear mixed models-principal component analysis.
Results:
The challenge meal explained most of the changes in the metabolome. The overall effect of L-arg supplementation significantly explained 0.5% of the total variance, irrespective of the response to the challenge meal (P < 0.05). Among the metabolites that explain most of the L-arg effect, we found many amino acids, including branched-chain amino acids, that were decreased by L-arg supplementation. L-arg also decreased trimethylamine N-oxide (TMAO). Other changes suggest that L-arg increased methyl demand.
Conclusions:
Analysis of the effect of 4 wk of L-arg supplementation on the metabolome reveals important effects on methyl balance and gut microbiota activity, such as a decrease in TMAO. Further studies are needed to investigate those mechanisms and the implications of these changes for long-term health.This trial was registered at clinicaltrials.gov as NCT02354794.
Related Concept Videos
Antianginal Drugs: Nitrates and β-Blockers
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow....
Exercise and Cardiovascular Response
Light to moderate physical activity initiates a series of interconnected responses in the body. The heart rate modestly increases in anticipation of the workout, followed by widespread vasodilation as oxygen consumption by skeletal muscles increases. This results in decreased peripheral resistance, increased capillary blood flow, and accelerated...
Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
Nitric Oxide Signaling Pathway
Exercise and Cardiac Output
Sustained exercise increases the muscles' oxygen demand, which can be...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

